Biogenesis and implication of miRNAs in the development of diseases and their theranostic inhibitions

Authors

Abstract

MicroRNAs (miRNAs), the naturally derived (canonical or non-canonical biogenesis) small non-coding RNAs linked to many crucial cellular processes and their dysregulations have emerged as the regulators of genes expression, mRNA translation, and proteins synthesis contributing to multiple pathological disease-progression and prognosis. Owing to the un-steadiness of miRNAs and their complex-degradation of mRNAs by nucleases and their dysregulated identifications in biological fluids as biomarkers for the development of diseases, miRNA mimics and anti-miRNAs molecules may be applied to restore miRNA expression or downregulate aberrantly expressed miRNAs as therapeutics loaded with delivery systems. This review denotes mainly the recent advances of the miRNA-based therapeutic delivery systems (such as viral, liposomal, exosomal and polymeric) as well as the novel strategies as emerging delivery systems (such as DNA origami, magnetosomes, micro needles and selenium nanoparticles) to diagnose and treat various diseases.

Keywords: miRNAs; Biogenesis; Biomarkers; Diseases; miRNA-based delivery systems; Novel strategies

Keywords:

miRNAs, Biogenesis, Biomarkers, Diseases, miRNA-based delivery systems, Novel strategies

DOI

https://doi.org/10.22270/jddt.v15i8.7336

Author Biographies

Ardhendu Kumar Mandal , Central Instrumentation Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India

Central Instrumentation Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India

Sunit Kumar Chakraborty , Department of Zoology, Raja Rammohun Roy Mahavidyalaya, Hooghly, India

Department of Zoology, Raja Rammohun Roy Mahavidyalaya, Hooghly, India

References

1. Boyd SD. Everything you wanted to know about small RNA but were afraid to ask. Lab Invest. 2008; 88:569-78. https://doi.org/10.1038/labinvest.2008.32

2. Bartel DP. Metazoan microRNAs. Cell. 2018; 173(1):20-51. https://doi.org/10.1016/j.cell.2018.03.006

3. Bartel DP. MicroRNAs: Genomica, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97. https://doi.org/10.1016/S0092-8674(04)00045-5

4. Qureshi A, Thakur N, Monga I, Thakur A, Kumar M. VIRmiRNA: A comprehensive resource for experimentally validated viral miRNAs and their targets. Database. 2014; bau 103. https://doi.org/10.1093/database/bau103

5. Rands CM, Meader S, Ponting CP, Lunter G. 8.2% of the human genome is constrained: Variation in rates of turnover across functional element classes in the human lineage. PLoS Genet. 2014; 10:e1004525. https://doi.org/10.1371/journal.pgen.1004525

6. Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, et al. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012; 489:57-74. https://doi.org/10.1038/nature11247

7. Halldorsson BV, Eggertsson HP, Moore KHS, Hauswedell H, Eiriksson O, Ulfarsson MO, et al. The sequences of 150,119 genomes in the UK Biobank. Nature. 2022; 607:732-40. https://doi.org/10.1038/s41586-022-04965-x

8. Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol. 2021; 22:96-118. https://doi.org/10.1038/s41580-020-00315-9

9. Alberti KGMM, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications Part 1: Diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabetic Med. 1999; 15:539-53. https://doi.org/10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S

10. Drury RE, O'Connor D, Pollard AJ. The clinical application of microRNAs in infectious disease. Front Immunol. 2017; 8:1182. https://doi.org/10.3389/fimmu.2017.01182

11. Lee TI, Young RA. Transcriptional regulation and its misregulation in disease. Cell. 2013; 152(6):1237-51. https://doi.org/10.1016/j.cell.2013.02.014

12. Finotti A, Fabbri E, Lampronti I, Gasparello J, Borgatti M, Gambari R. MicroRNAs and long non-coding RNAs in genetic diseases. Mol Diagn Ther. 2019; 23:155-71. https://doi.org/10.1007/s40291-018-0380-6

13. Markopoulos GS, Roupakia E, Tokamani M, Alabasi G, Sandaltzopoulos R, Marcu KB, et al. Roles of NF-kappa B signaling in the regulation of miRNAs impacting on inflammation in cancer. Biomedicines. 2018; 6:40. https://doi.org/10.3390/biomedicines6020040

14. McCoy CE. MiR-155 dysregulation and therapeutic intervention in multiple sclerosis. Adv Exp Med Biol. 2017; 1024:111-31. https://doi.org/10.1007/978-981-10-5987-2_5

15. Miya Shaik M, Tamargo IA, Abubakar MB, Kamal MA, Greig NH, Gan SH. The role of microRNAs in Alzheimer's disease and their therapeutic potentials. Genes. 2018; 9:174. https://doi.org/10.3390/genes9040174

16. Strumidlo A, Skiba S, Scott RJ, Lubinski J. The potential role of miRNAs in therapy of breast and ovarian cancers associated with BRCA1 mutation. Hered Cancer Clin Pract. 2017; 15:15. https://doi.org/10.1186/s13053-017-0076-7

17. Wojciechowska A, Braniewska A, Kozar-Kaminska K. MicroRNA in cardiovascular biology and disease. Adv Clin Exp Med. 2017; 26:865-74. https://doi.org/10.17219/acem/62915

18. Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee SU. Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac J Cancer Prev. 2017; 18(1):3.

19. Khraiwesh B, Arif MA, Seumel GI, Ossowski S, Weigel D, Reski R, et al. Transcriptional control of gene expression by microRNAs. Cell. 2010; 140:111-22. https://doi.org/10.1016/j.cell.2009.12.023

20. Samad AFA, Sajad M, Nazaruddin N, Fauzi IA, Murad AMA, Zainal Z, et al. MicroRNA and transcription factor: Key players in plant regulatory network. Front Plant Sci. 2017; 8:565. https://doi.org/10.3389/fpls.2017.00565

21. Tong Z, Cui Q, Wang J, Zhou Y. TransmiRv2.0: An updated transcription factor-microRNA regulation database. Nucleic Acids Res. 2018; 47:D253-D258. https://doi.org/10.1093/nar/gky1023

22. Seyhan AA. MicroRNAs with different functions and roles in disease development and as potential biomarkers of diabetes: Progress and challenges. Mol Biosyst. 2015; 11:1217-34. https://doi.org/10.1039/C5MB00064E

23. Chen PY, Meister G. MicroRNA-guided post transcriptional gene regulation. Biol Chem. 2005; 386:1205-18. https://doi.org/10.1515/BC.2005.139

24. Catalanotto C, Cogoni C, Zardo G. MicroRNA in control of gene expression: An overview of nuclear functions. Int J Mol Sci. 2016; 17:1712. https://doi.org/10.3390/ijms17101712

25. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of action, and circulation. Front Endocrinol. 2018; 9:402. https://doi.org/10.3389/fendo.2018.00402

26. Wang H, Meng Q, Qian J, Li M, Gu C, Yang Y. Review: RNA-based diagnostic markers discovery and therapeutic targets development in cancer. Pharmacol Ther. 2022; 234:108123. https://doi.org/10.1016/j.pharmthera.2022.108123

27. Guo Z, Maki M, Ding R, Yang Y, Zhang B, Xiong L. Genome-wide survey of tissue-specific microRNA and transcription factor regulatory networks in 12 tissues. Sci Rep. 2014; 4:5150. https://doi.org/10.1038/srep05150

28. Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, deBruijn E, et al. MicroRNA expression in zebrafish embryonic development. Science. 2005; 309:310-11. https://doi.org/10.1126/science.1114519

29. Aboobaker AA, Tomancak P, Patel N, Rubin GM, Lai EC. Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development. Proc Natl Acad Sci USA. 2005; 102:18017-22. https://doi.org/10.1073/pnas.0508823102

30. Walker JC, Harland RM. Expression of microRNAs during embryonic development of Xenopus tropicalis. Gene Expr Patterns. 2008; 8:452-56. https://doi.org/10.1016/j.gep.2008.03.002

31. Gareev I, de Jesus Encarnacion Ramirez M, Goncharov E, Ivliev D, Shumadalova A, Ilyasova T, et al. MiRNAs and loncRNAs in the regulation of innate immune signaling. Noncoding RNA Res. 2023; 8:534-41. https://doi.org/10.1016/j.ncrna.2023.07.002

32. Pauley KM, Cha S, Chan EK. MicroRNA in autoimmunity and autoimmune diseases. J Autoimmune. 2009; 32:189-94. https://doi.org/10.1016/j.jaut.2009.02.012

33. Elfimova N, Schlattjan M, Sowa JP, Dienes HP, Canbay A, Odenthal M. Circulating microRNAs: Promising candidates serving as novel biomarkers of acute hepatitis. Front Physiol. 2012; 3:476. https://doi.org/10.3389/fphys.2012.00476

34. Scott KA, Hoban AE, Clarke G, Moloney GM, Dinan TG, Cryan JF. Thinking small: Towards microRNA-based therapeutics for anxiety disorders. Expert Opin Investig Drugs. 2015; 24:529-42. https://doi.org/10.1517/13543784.2014.997873

35. Li YJ, Xu M, Gao ZH, Wang YQ, Yue Z, Zhang YX, et al. Alterations of serum levels of BDNF-related miRNAs in patients with depression. PLoS One. 2013; 8:e63648. https://doi.org/10.1371/journal.pone.0063648

36. Weir DW, Sturrock A, Leavitt BR. Development of biomarkers for Huntington's disease. Lancet Neurol. 2011; 10:573-90. https://doi.org/10.1016/S1474-4422(11)70070-9

37. Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014; 15:509-24. https://doi.org/10.1038/nrm3838

38. Broughton JP, Lovci MT, Huang JL, Yeo GW, Pasquinelli AE. Pairing beyond the seed supports microRNA targeting specificity. Mol Cell. 2016; 64:320-33. https://doi.org/10.1016/j.molcel.2016.09.004

39. Vasudevan S. Post transcriptional upregulation by microRNAs. Wiley Interdiscip Rev RNA. 2012; 3:311-30. https://doi.org/10.1002/wrna.121

40. Makarova JA, Shkurnikov MU, Wicklein D, Lange T, Samatov TR, Turchinovich AA, et al. Intracellular and extracellular microRNA: An update on localization and biological role. Prog Histochem Cytochem. 2016; 51:33-49. https://doi.org/10.1016/j.proghi.2016.06.001

41. Fu G, Brkic J, Hayder H, Peng C. MicroRNAs in human placental development and pregnancy complications. Int J Mol Sci. 2013; 14:5519-44. https://doi.org/10.3390/ijms14035519

42. Tufekci KU, Oner MG, Meuwissen RL, Genc S. The role of microRNAs in human diseases. Methods Mol Biol. 2014; 1107:33-50. https://doi.org/10.1007/978-1-62703-748-8_3

43. Paul P, Chakraborty A, Sarkar D, Langthasa M, Rahman M, Bari M, et al. Interplay between miRNAs and human diseases. J Cell Physiol. 2018; 233:2007-18. https://doi.org/10.1002/jcp.25854

44. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, et al. Detection of elevated levels of tumor-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008; 141(5):672-5. https://doi.org/10.1111/j.1365-2141.2008.07077.x

45. Chen X, Ba Y, Ma L, Cai X, Vin Y, Wang K, et al. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008; 18(10): 997-1006. https://doi.org/10.1038/cr.2008.282

46. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by hugh-density lipoproteins. Nat Cell Biol. 2011; 13(4):432-33. https://doi.org/10.1038/ncb2210

47. Skog J, Wurdinger T, van Rijin S, Meijer DH, Gainche L, Sena-Esteves M, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumor growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10(12): 1470-6. https://doi.org/10.1038/ncb1800

48. Jung HJ, Suh Y. Circulating miRNAs in aging and aging-related diseases. J Gent Genomics. 2014; 41(9):465-72. https://doi.org/10.1016/j.jgg.2014.07.003

49. Zhang L, Hou D, Chen X, Li D, Zhu L, Zhang Y, et al. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: Evidence of cross-kingdom regulation by microRNA. Cell Res. 2012; 22:107-26. https://doi.org/10.1038/cr.2011.158

50. Witwer KW. XenomiRs and miRNA homeostasis in health and disease: Evidence that diet and dietary miRNAs directly and indirectly influence circulating miRNA profiles. RNA Biol. 2012; 9:1147-54. https://doi.org/10.4161/rna.21619

51. Wagner AE, Piegholdt S, Ferraro M, Pallauf K, Rimbach G. Food derived microRNAs. Food Funct. 20915; 6:714-8. https://doi.org/10.1039/C4FO01119H

52. Zhang L, Chen T, Yin Y, Zhang CY, Zhang YL. Dietary microRNA-A novel functional component of food. Adv Nutr. 2019; 10:711-21. https://doi.org/10.1093/advances/nmy127

53. Diez-Sainz E, Lorente-Cebrian S, Aranaz P, Riezu-Boj JI, Martinez JA, Milagro FI. Potential mechanisms linking food-derived microRNAs, gut microbiota and intestinal barrier functions in the context of nutrition and human health. Front Nutr. 2021; 8:586564. https://doi.org/10.3389/fnut.2021.586564

54. Cieslik M, Bryniarski K, Nazimek K. Dietary and orally-delivered miRNAs: Are they functional and ready to modulate immunity? AIMS Allergy Immunol. 2023; 7:104-31. https://doi.org/10.3934/Allergy.2023008

55. Ali Syeda Z, Langden SSS, Munkhzul C, Lee M, Song SJ. Regulatory mechanism of microRNA expression in cancer. Int J Mol Sci. 2020; 21:1723. https://doi.org/10.3390/ijms21051723

56. Arif KMT, Elliott EK, Haupt LM, Griffiths LR. Regulatory mechanisms of epigenetic miRNA relationships in human cancer and potential as therapeutic targets. Cancers. 2020; 12:2922. https://doi.org/10.3390/cancers12102922

57. Machowska M, Galka-Marciniak P, Kozlowski P. Consequences of genetic variants in miRNA genes. Comput Struct Biotechnol J. 2022; 20:6443-57. https://doi.org/10.1016/j.csbj.2022.11.036

58. Bortoletto AS, Parchem RJ. KRAS hijacks the miRNA regulatory pathway in cancer. Cancer Res. 2023; 83:1563-72. https://doi.org/10.1158/0008-5472.CAN-23-0296

59. Tan L, Yu JT, Hu N, Tan L. Non-coding RNAs in Alzheimer's disease. Mol Neurobiol. 2013; 135:479-80. https://doi.org/10.1007/s12035-012-8359-5

60. Hershkovitz-Rokah O, Modai S, Pasmanik-Chor M, Toren A, Shomron N, Raanani P, et al. MiR-30e induces apoptosis and sensitizes K562 cells to imatinib treatment via regulation of the BCR-ABL protein. Cancer Lett. 2015; 356:597-605. https://doi.org/10.1016/j.canlet.2014.10.006

61. Petrescu GE, Sabo AA, Torsin LI, Calin GA, Dragomir MP. MicroRNA based theranostics for brain cancer: Basic principles. J Exp Clin Cancer Res. 2019; 38(1):1-21. https://doi.org/10.1186/s13046-019-1180-5

62. Anthiya S, Griveau A, Loussouarn C, Baril P, Garnett M, Issartel JP, et al. MicroRNA-based drugs for brain tumors. Trends Cancer. 2018; 4(3):222-38. https://doi.org/10.1016/j.trecan.2017.12.008

63. Nafee N, Gouda N. Nucleic acids-based nanotherapeutics crossing the blood brain barrier. Curr Gene Ther. 2017; 17(2):154-69. https://doi.org/10.2174/1566523217666170510155803

64. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol. 2018; 9:402. https://doi.org/10.3389/fendo.2018.00402

65. Hammond SM. An overview of microRNAs. Adv Drug Deliv Rev. 2015; 87:3-14. https://doi.org/10.1016/j.addr.2015.05.001

66. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73. https://doi.org/10.1038/nature03315

67. Olsen PH, Ambros V. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol. 1999; 216(2):671-80. https://doi.org/10.1006/dbio.1999.9523

68. Vasudevan S, Tong YC, Steitz JA. Switching from repression to activation: MicroRNAs can up-regulate translation. Science. 2007; 318(5858):1931-4. https://doi.org/10.1126/science.1149460

69. Gomez A, Ingelman-Sundberg M. Epigenetic and microRNA-dependent control of cytochrome P450 expression: A gap between DNA and protein. Pharmacogenomics. 2009; 10:1067-76. https://doi.org/10.2217/pgs.09.56

70. Johansson I, Ingelman-Sundberg M. Genetic polymorphism and toxicology with emphasis on cytochrome P450. Toxicol Sci. 2011; 120:1-13. https://doi.org/10.1093/toxsci/kfq374

71. Yu AM, Tian Y, Tu MJ, Ho PY, Jilek J. MicroRNA pharmaco-epigenetics: Post-transcriptional regulation mechanisms behind variable drug disposition and strategy to develop more effective therapy. Drug Metab Dispos. 2016; 44(3):308-19. https://doi.org/10.1124/dmd.115.067470

72. Li D, Tolleson WH, Yu D, Chen Si, Guo L, Xiao W, et al. Regulation of cytochrome P450 expression by microRNAs and long noncoding RNAs: Epigenetic mechanisms in environmental toxicology and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxical Rev. 2019; 37(3):180-214. https://doi.org/10.1080/10590501.2019.1639481

73. Yu AM, Pan YZ. Noncoding microRNAs: Small RNAs play a big role in regulation of ADME? Acta Pharm Sin B. 2012: 2:93-101. https://doi.org/10.1016/j.apsb.2012.02.011

74. Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KLR, Chu X, et al. Membrane transporters in drug development. Nat Rev Drug Discov. 2010; 9(3):215-36. https://doi.org/10.1038/nrd3028

75. Ikemura K, Iwamoto T, Okuda M. MicroRNAs as regulators of drug transporters, drug-metabolizing enzymes, and tight junctions: Implication for intestinal barrier function. Pharmacol Ther. 2014; 143:217-24. https://doi.org/10.1016/j.pharmthera.2014.03.002

76. Kalscheuer S, Zhang X, Zeng Y, Upadhyaya P. Differential expression of microRNAs in early-stage neoplastic transformation in the lungs of F344 rats chronically treated with the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Carcinogenesis. 2008; 29:2394-99. https://doi.org/10.1093/carcin/bgn209

77. Komagata S, Nakajima M, Takagi S, Mohri T, Taniya T, Yokoi T. Human CYP24 catalyzing the inactivation of calcitriol is post-transcriptionally regulated by miR-125b. Mol Pharmacol. 2009; 76(4):702-9. https://doi.org/10.1124/mol.109.056986

78. Song KH, Li T, Owsley E, Chiang JYL. A putative role of microRNA in regulation of cholesterol 7a-hydroxylase expression in human hepatocytes. J Lipid Res. 2010; 51:2223-33. https://doi.org/10.1194/jlr.M004531

79. Toscano-Garibay JD, Aquino-Jarquin G. Regulation exerted by miRNAs in the promoter and UTR sequences: MDR1/P-gp expression as a particular case. DNA Cell Biol. 2012; 31:1358-64. https://doi.org/10.1089/dna.2012.1703

80. Zhu H, Wu H, Liu X, Evans BR, Medina DJ, Liu CG, et al. Role of microRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem Pharmacol. 2008; 76(5):582-8. https://doi.org/10.1016/j.bcp.2008.06.007

81. Dong Z, Zhong Z, Yang L, Wang S, Gong Z. MicroRNA-31 inhibits cisplatin-induced apoptosis in non-small cell lung cancer cells by regulating the drug transporter ABCB9. Cancer Lett. 2014; 343(2):249-57. https://doi.org/10.1016/j.canlet.2013.09.034

82. Pan YZ, Zhou A, Hu Z, Yu AM. Small nucleolar RNA-derived microRNA has-miR-1291 modulates cellular drug disposition through direct targeting of ABC transporter ABCC1. Drug Metab Dispos. 2013; 41(10):1744-51. https://doi.org/10.1124/dmd.113.052092

83. Chen KC, His E, Hu CY, Chou WW, Liang CL, Juo SHH. MicroRNA-328 may influence myopia development by mediating the PAX6 gene. Investig Ophthalmol Vis Sci. 2012; 53(6):2732-9. https://doi.org/10.1167/iovs.11-9272

84. Jeon HM, Sohn YW, Oh SY, Kim SH, Beck S, Kim S, et al. ID4 imparts chemoresistance and cancer stemness to glioma cells by derepressing miR-9-mediated suppression of SOX2. Cancer Res. 2011; 71(9):3410-21. https://doi.org/10.1158/0008-5472.CAN-10-3340

85. Zhu Y, Yu F, Jiao Y, Feng J, Tang K, Yao H, et al. Reduced miR-128 in breast tumor-initiating cells induces chemotherapeutic resistance via Bmi-1 and ABCC5. Clin Cancer Res. 2011; 17(22):7105-15. https://doi.org/10.1158/1078-0432.CCR-11-0071

86. Bruhn O, Lindsay M, Wiebel F, Kaehler M, Nagel I, Bohm R, et al. Alternative polyadenylation of ABC transporters of the C-family (ABCC1, ABCC2, ABCC3) and implications on post transcriptional micro-RNA regulations. Mol Pharmacol. 2020; 97(2):112-22. https://doi.org/10.1124/mol.119.116590

87. Zhu H, Ng SC, Segr AV, Shinoda G, Shah SP, Einhorn WS, et al. The Lin 28/let-7 axis regulates glucose metabolism. Cell. 2011; 147:81-94. https://doi.org/10.1016/j.cell.2011.08.033

88. Frost RJA, Olson EN. Control of glucose homeostasis and insulin sensitivity by the let-7 family of microRNAs. Proc Natl Acad Sci USA. 2011; 108: 21075-80. https://doi.org/10.1073/pnas.1118922109

89. Ling HY, Wen GB, Feng SD, Tuo QH, Ou HS, Yao CH, et al. MicroRNA-375 promotes 3T3-L1 adipocyte differentiation through modulation of extracellular signal-regulated kinase signaling. Clin Exp Pharmacol Physiol. 2011; 38:239. https://doi.org/10.1111/j.1440-1681.2011.05493.x

90. Yang F, Wang Y, Xue J, Ma Q, Zhang J, Chen YF, et al. Effect of corilagin on the miR-21/smad7/ERK signaling pathway in a Schistosomiasis-induced hepatic fibrosis mouse model. Parasitol Int. 2016; 65:308-15. https://doi.org/10.1016/j.parint.2016.03.001

91. Jing E, Gesta S, Kahn CR. SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. Cell Metab. 2007; 6:105-14. https://doi.org/10.1016/j.cmet.2007.07.003

92. Kennell JA, Gerin I, MacDougald OA, Cadigan KM. The microRNAmiR-8 is a conserved negative regulator of Wnt signaling. Proc Natl Acad Sci USA. 2008; 105:15417-22. https://doi.org/10.1073/pnas.0807763105

93. Liang WC, Wang Y, Wan DCC, Yeung VSY, Waye MMY. Characterization of miR-210 in 3T3-L1 adipogenesis. J Cell Biochem. 2013; 114: 2699-707. https://doi.org/10.1002/jcb.24617

94. Ortega FJ, Moreno-Navarrete JM, Pardo G, Sabater M, Hummel M, Ferrer A, et al. MiRNA expression profile of human subcutaneous adipose and during adipocyte differentiation. PLoS ONE. 2010; 2:e9022. https://doi.org/10.1371/journal.pone.0009022

95. Thompson MD, Cismowski MJ, Serpico M, Pusateri A, Brigstock DR. Elevation of circulating microRNA levels in obese children compared to healthy controls. Clin Obes. 2017; 7:216-21. https://doi.org/10.1111/cob.12192

96. Shi XE, Li YF, Jia L, Ji HL, Song ZY, Cheng J, et al. MicroRNA-199a-5p affects porcine preadipocyte proliferation and differentiation. Int J Mol Sci. 2014; 15:8526-38. https://doi.org/10.3390/ijms15058526

97. Pang H, Zheng Y, Zhao Y, Xiu X, Wang J. MiR-590-3p suppresses cancer cell migration, invasion and epithelial mesenchymal transition in glioblastoma multiforme by targeting ZEB1 and ZEB2. Biochem Biophys Res Commun. 2015; 468:739-45. https://doi.org/10.1016/j.bbrc.2015.11.025

98. Xu P, Vernooy SY, Guo M, Hay BA. The drosophila microRNA miR-14 suppresses cell death and is required for normal fat metabolism. Curr Biol. 2003; 13:790-5. https://doi.org/10.1016/S0960-9822(03)00250-1

99. Rotllan N, Price N, Pati P, Goedeke L, Fernandez-Hernando C. MicroRNAs in lipoprotein metabolism and cardiometabolic disorders. Atherosclerosis. 2016; 246: 352-60. https://doi.org/10.1016/j.atherosclerosis.2016.01.025

100. Karbiener M, Neuhold C, Opriessnig P, Prokesch A, Scheideler M. MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1and ALK2. RNA biol. 2011; 8:1-11. https://doi.org/10.4161/rna.8.5.16153

101. Yang WM, Jeong HJ, Park SY, Lee W. Induction of miR-29a by saturated fatty acids impairs insulin signaling and glucose uptake through translational repression of IRS-1 in myocytes. FEBS Lett. 2014; 588:2170-6. https://doi.org/10.1016/j.febslet.2014.05.011

102. Zhang Y, Yang L, Gao YF, Fan ZM, Cai XY, Liu MY, et al. MicroRNA-106b induces mitochondrial dysfunction and insulin resistance in C2C12 myotubes by targeting mitofusin-2. Mol Cell Endocrinol. 2013; 381:230-40. https://doi.org/10.1016/j.mce.2013.08.004

103. Ortega FJ, Mercader JM, Moreno-Navarrete JM, Rovira O, Guerra E, Esteve E, et al. Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization. Diabetes care. 2014; 37:1375-83. https://doi.org/10.2337/dc13-1847

104. Ghorbani S, Mahdavi R, Alipoor B, Panahi G, Nasli Esfahani E, Razi F, et al. Decreased serum microRNA-21 level is associated with obesity in healthy and type 2 diabetic subjects. Arch Physiol Biochem. 2018; 124:300-5. https://doi.org/10.1080/13813455.2017.1396349

105. Donghui T, Shuang B, Xulong L, Meng Y, Yujing G, Yujie H, et al. Improvement of microvascular endothelial dysfunction induced by exercise and diet is associated with microRNA-126 in obese adolescents. Microvasc Res. 2019; 123:86-91. https://doi.org/10.1016/j.mvr.2018.10.009

106. Asangani IA, Rasheed SAK, Nikolova DA, Leupold JH, Colburn NH, Post S, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008; 27:2128-36. https://doi.org/10.1038/sj.onc.1210856

107. Villard A, Marchand L. Diagnostic value of cell-free circulating microRNAs for obesity and type 2 diabetes: A meta-analysis. J Mol Biomark Diagn. 2015; 6:251. https://doi.org/10.4172/2155-9929.1000251

108. Shi C, Zhang M, Tong M, Yang L, Pang L, Chen L, et al. MiR-148a is associated with obesity and modulates adipocyte differentiation of mesenchymal stem cells through Wnt signaling. Sci Rep. 2015; 5:9930. https://doi.org/10.1038/srep09930

109. Jordan SD, Kruger M, Willmes DM, Redemann N, Wunderlich FT, Bronneke HS, et al. Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism. Nat Cell Biol. 2011; 13:434-46. https://doi.org/10.1038/ncb2211

110. Zaiou M, El Amri H, Bakillah A. The clinical potential of adipogenesis and obesity-related microRNAs. Nutr Metab Cardiovasc Dis. 2018; 28:91-111. https://doi.org/10.1016/j.numecd.2017.10.015

111. Zeisel MB, Pfeffer S, Baumert TF, Perle LK, J GK. MiR-122 acts as a tumor suppressor in hepatocarcinogenesis in vivo. J Hepatol. 2013; 58:821-3. https://doi.org/10.1016/j.jhep.2012.10.010

112. Chen L, Cui J, Hou J, Long J, Li C, Liu L. A novel negative regulator of adipogenesis: MicroRNA-363. Stem Cells. 2014; 32:510-20. https://doi.org/10.1002/stem.1549

113. Butler AE, Dhawan S. β-cell identity in type 2 diabetes: Lost or found? Diabetes. 2015; 64:2698-700. https://doi.org/10.2337/db15-0550

114. Wang N, Zhang LM, Lu Y, Zhang MX, Zhang ZN, Wang K, et al. Down-regulation of microRNA-142-5p attenuates oxygen-glucose deprivation and reoxygenation-induced neuron injury through up-regulating Nrf2/ARE signaling pathway. Biomed Pharmacother. 2017; 89:1187-95. https://doi.org/10.1016/j.biopha.2017.03.011

115. Chu XL, Wang YQ, Pang LW, Huang JC, Sun XT, Chen XF. MiR-130 aggravates acute myocardial infarction-induced myocardial injury by targeting PPAR-γ. J Cell Biochem. 2018; 119:7235-44. https://doi.org/10.1002/jcb.26903

116. Singaravelu R, Chen R, Lyn RK, Jones DM, O'Hara S, Rouleau Y, et al. Hepatitis C virus induced up-regulation of microRNA-27: A novel mechanism for hepatic steatosis. Hepatol. 2014; 59:98-108. https://doi.org/10.1002/hep.26634

117. Al-Rawaf HA. Circulating microRNAs and adipokines as markers of metabolic syndrome in adolescents with obesity. Clin Nutr. 2019; 38:2231-8. https://doi.org/10.1016/j.clnu.2018.09.024

118. Ortega FJ, Mercader JM, Catalan V, Moreno-Navarrete JM, Pueyo N, Sabater M, et al. Targeting the circulating microRNA signature of obesity. Clin Chem. 2013; 59:781-92. https://doi.org/10.1373/clinchem.2012.195776

119. Baskin KK, Winders BR, Olson EN. Muscle as a "mediator" of systemic metabolism. Cell Metab. 2015; 21:237-48. https://doi.org/10.1016/j.cmet.2014.12.021

120. Baskin KK, Grueter CE, Kusminski CM, Holland WL, Bookout AL, Satapati S, et al. MED13-dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver. EMBO Mol Med. 2014; 6:1610-21. https://doi.org/10.15252/emmm.201404218

121. Novak J, Vasku JB, Kara T, Novak M. Micro RNAs involved in the lipid metabolism and their possible implications for atherosclerosis development and treatment. Mediat Inflamm. 2014; 275867. https://doi.org/10.1155/2014/275867

122. Zaragosi LE, Wdziekonski B, Brigand KL, Villageis P, Mari B, Waldmann R, et al. Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis. Genome Biol. 2011; 12:R64. https://doi.org/10.1186/gb-2011-12-7-r64

123. Wang J, Guan X, Guo F, Zhou J, Chang A, Sun B, et al. MiR-30e reciprocally regulates the differentiation of adipocytes and osteoblasts by directly targeting low-density lipoprotein receptor-related protein 6. Cell Death Dis. 2013; 4:e845. https://doi.org/10.1038/cddis.2013.356

124. Vickers KC, Landstreet SR, Levin MG, Shoucri BM, Toth CL, Taylor RC, et al. MicroRNA-223 coordinates cholesterol homeostasis. Proc Natl Acad Sci USA. 2014; 111:14518-23. https://doi.org/10.1073/pnas.1215767111

125. Hyun S, Lee JH, Jin H, Nam JW, Namkoong B, Lee G, et al. Conserved microRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K. Cell. 2009; 139:1096-108. https://doi.org/10.1016/j.cell.2009.11.020

126. Kredo-Russo S, Mandelbaum AD, Ness A, Alon I, Lennox KA, Behlke MA, et al. Pancreas-enriched miRNA refines endocrine cell differentiation. Development. 2012; 139:3021-31. https://doi.org/10.1242/dev.080127

127. Vickers KC, Shoucri BM, Levin MG, Wu H, Pearson DS, Osei-Hwedieh D, et al. MicroRNA-27b is a regulatory Hub in lipid metabolism and is altered in dyslipidemia. Hepatol. 2013; 57:533-42. https://doi.org/10.1002/hep.25846

128. Zhong D, Huang G, Zhang Y, Zeng Y, Xu Z, Zhao Y, et al. MicroRNA-1 and microRNA-206 suppress LXRα-induced lipogenesis in hepatocytes. Cell Signal. 2013; 25:1429-37. https://doi.org/10.1016/j.cellsig.2013.03.003

129. Qin L, Chen Y, Niu Y, Chen W, Wang Q, Xiao S, et al. A deep investigation into the adipogenesis mechanism: Profile of microRNAs regulating adipogenesis by modulating the canonical Wnt/β-catenin signaling pathway. BMC Genom. 2010; 11:320. https://doi.org/10.1186/1471-2164-11-320

130. Hilton C, Neville MJ, Karpe F. MicroRNAs in adipose tissue: Their role in adipogenesis and obesity. Int J Obes. 2013; 37:325-32. https://doi.org/10.1038/ijo.2012.59

131. Shaer A, Azarpira N, Vahdati A, Karimi MH, Shariati M. MiR-375 induces human deciduas basalis-derived stromal cells to become insulin-producing cells. Cell Mol Biol. 2014; 19:483-99. https://doi.org/10.2478/s11658-014-0207-3

132. Belarbi Y, Mejhert N, Lorente-Cebrian S, Dahlman I, Arner P, Ryden M, et al. MicroRNA-193b controls adiponectin production in human white adipose tissue. J Clin Endocrinol Metab. 2015; 100:E1084-8. https://doi.org/10.1210/jc.2015-1530

133. Jeong BC, Kang IH, Hwang YC, Kim SH, Koh JT. MicroRNA-194 reciprocally stimulates osteogenesis and inhibits adipogenesis via regulating COUP-TFII expression. Cell Death Dis. 2014; 5:e1532. https://doi.org/10.1038/cddis.2014.485

134. Peng Y, Xiang H, Chen C, Zheng R, Chai J, Peng J, et al. MiR-224 impairs adipocyte early differentiation and regulates fatty acid metabolism. Int J Biochem Cell Biol. 2013; 8:1585-93. https://doi.org/10.1016/j.biocel.2013.04.029

135. Zhang JF, Fu WM, He ML, Wang H, Wang WM, Yu SC, et al. MiR-637 maintains the balance between adipocytes and osteoblasts by directly targeting osterix. Mol Biol Cell. 2011; 22:3955-61. https://doi.org/10.1091/mbc.e11-04-0356

136. Yang Z, Bian C, Zhou H, Huang S, Wang S, Liao L, et al. MicroRNA Has-miR-138 inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells through adenovirus EID-1. Stem Cell Dev. 2011; 20:259-67. https://doi.org/10.1089/scd.2010.0072

137. Trans EG, Lauter CJ, Norman Salem J, Heine U. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. BBA Biomembr. 1981; 645:63-70. https://doi.org/10.1016/0005-2736(81)90512-5

138. Gong M, Yu B, Wang J, Wang Y, Liu M, Paul C, et al. Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogenesis. Oncotarget. 2017; 8:45200-12. https://doi.org/10.18632/oncotarget.16778

139. Yamada Y, Enokida H, Kojima S, Kawakami K, Chiyomaru T, Tatarano S, et al. MiR-96 and MiR-183 detection in urine serve as potential tumor markers of urothelial carcinoma: Correlation with stage and grade, and comparison with urinary cytology. Cancer Sci. 2011; 102:522-9. https://doi.org/10.1111/j.1349-7006.2010.01816.x

140. Sun L, Xu R, Sun X, Duan Y, Han Y, Zhao Y, et al. Safety evaluation of exosomes derived from human umbilical cord mesenchymal stromal cell. Cytother. 2016; 18:413-22. https://doi.org/10.1016/j.jcyt.2015.11.018

141. Thomou T, Mori MA, Dreyfuss JM, Konishi M, Sakaguchi M, Wolfrum C, et al. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 2017; 542:450-5. https://doi.org/10.1038/nature21365

142. Li GL, Ning CY, Ma Y, Jin L, Tang QZ, Li XW, et al. MiR-26b promotes 3T3-L1 adipocyte differentiation through targeting PTEN. DNA Cell Biol. 2017; 36:672-81. https://doi.org/10.1089/dna.2017.3712

143. Kinoshita M, Ono K, Horie T, Nagao K, Nishi H, Kuwabara Y, et al. Regulation of adipocyte differentiation by activation of serotonin (5-HT) receptors 5-HT2AR and 5-HT2CR and involvement of microRNA-448-mediated repression of KLF5. Mol Endocrinol. 2010; 24:1978-87. https://doi.org/10.1210/me.2010-0054

144. Skarn M, Namlos HM, Noordhuis P, Wang MY, Meza-Zepeda LA, Myklebost O. Adipocyte differentiation of human bone marrow-derived stromal cells is modulated by microRNA-155, microRNA-221, and microRNA-222. Stem Cells Dev. 2012; 21:873-83. https://doi.org/10.1089/scd.2010.0503

145. Rani P, Vashisht M, Golla N, Shandilya S, Onteru SK, Singh D. Milk miRNAs encapsulated in exosomes are stable to human digestion and permeable to intestinal barrier in vitro. J Funct Foods. 2017; 34:431-9. https://doi.org/10.1016/j.jff.2017.05.009

146. Zhang H, Wu J, Wu J, Fan Q, Zhou J, Wu J, et al. Exosome-mediated targeted delivery of miR-210 for angiogenic therapy after cerebral ischemia in mice. J Nanobiotechnol. 2019; 17:29. https://doi.org/10.1186/s12951-019-0461-7

147. Zhi Y, Xu C, Sui D, Du J, Xu FJ, Li Y. Effective delivery of hypertrophic miRNA inhibitor by cholesterol-containing nanocarriers for preventing pressure overload induced cardiac hypertrophy. Adv Sci. 2019; 6:1900023. https://doi.org/10.1002/advs.201900023

148. Kang JY, Park H, Kim H, Mun D, Park H, Yun N, et al. Human peripheral blood-derived exosomes for microRNA delivery. Int J Mol Med. 2019; 43:2319-28. https://doi.org/10.3892/ijmm.2019.4150

149. Maryam T, Hossein H, Maryam S, Mehdi K, Farshid N, Reza M. Inhibiting miR-27a and miR-142-5p attenuate nonalcoholic fatty liver disease by regulating Nrf2 signaling pathway. IUBMB Life. 2020; 72:361-72. https://doi.org/10.1002/iub.2221

150. Guo Y, Chen Y, Zhang Y, Zhang Y, Chen L, Mo D. Up-regulated miR-145 expression inhibits porcine preadipocytes differentiation by targeting IRS1. Int J Biol Sci. 2012; 8:1408-17. https://doi.org/10.7150/ijbs.4597

151. Castasso C, Kalko S, Novials A, Parrizas M. Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice. Proc Natl Acad Sci USA. 2018; 115:12158-63. https://doi.org/10.1073/pnas.1808855115

152. Chen H, Mo D, Li M, Zhang Y, Chen L, Zhang X, et al. MiR-709 inhibits 3T3-L1 cell differentiation by targeting GSK3β of Wnt/β-catenin signaling. Cell Signal. 2014; 26:2583-9. https://doi.org/10.1016/j.cellsig.2014.07.017

153. Ying W, Riopel M, Bandyopadhyay G, Dong Y, Birmingham A, Seo JB, et al. Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity. Cell. 2017; 171:372-84. https://doi.org/10.1016/j.cell.2017.08.035

154. Maja L, Zeljko K, Mateja P. Sustainable technologies for liposome preparation. J Supercrit Fluids. 2020; 165:104984. https://doi.org/10.1016/j.supflu.2020.104984

155. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceut. 2018; 10:57. https://doi.org/10.3390/pharmaceutics10020057

156. Cioffi M, Vallespinos-Serrano M, Trabulo SM, Fernandez-Marcos PJ, Firment AN, Vazquez BN, et al. MiR-93 controls adiposity via inhibition of Sirt 7 and Tbx3. Cell Rep. 2015; 12:1594-605. https://doi.org/10.1016/j.celrep.2015.08.006

157. Li M, Liu Z, Zhang Z, Liu G, Sun S, Sun C. MiR-103 promotes 3T3-L1 cell adipogenesis through AKT/mTOR signal pathway with its target being MEF2D. Biol Chem. 2015; 396:235-44. https://doi.org/10.1515/hsz-2014-0241

158. Ong SGM, Chitnani M, Lee KS, Ming LC, Yuen KH. Evaluation of extrusion technique for nanosizing liposomes. Pharmaceut. 2016; 8:36. https://doi.org/10.3390/pharmaceutics8040036

159. Dong Y, Love KT, Dorkin JR, Sirirungruang S, Zhang Y, Chen D, et al. Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates. Proc Natl Acad Sci USA. 2014; 111:3955-60. https://doi.org/10.1073/pnas.1322937111

160. Zhang Z, Fang X, Hao J, Li Y, Sha X. Triolein-based polycation lipid nanocarrier for efficient gene delivery: Characteristics and mechanism. Int J Nanomed. 2011; 6:2235-44. https://doi.org/10.2147/IJN.S24720

161. Marsh D, Bartucci R, Sportelli L. Lipid membranes with grafted polymers: Physicochemical aspects. BBA Biomembr. 2003; 1615:33-59. https://doi.org/10.1016/S0005-2736(03)00197-4

162. Liu M, Li M, Sun S, Li B, Du D, Sun J, et al. The use of antibody modified liposomes loaded with AMO-1 to deliver oligonucleotides to ischemic myocardium for arrhythmia therapy. Biomater. 2014; 35:3697-707. https://doi.org/10.1016/j.biomaterials.2013.12.099

163. Koide H, Asai T, Hatanaka K, Akai S, Ishii T, Kenjo E, et al. T cell-independent B cell response is responsible for ABC phenomenon induced by repeated injection of PEGylated liposomes. Int J Pharm. 2010; 392:218-23. https://doi.org/10.1016/j.ijpharm.2010.03.022

164. Jeong Kim Y, Jin Hwang S, Chan Bao Y, Sup Jung J. MiR-21 regulates adipogenic differentiation through the modulation of TGF-β signaling in mesenchymal stem cells derived from human adipose tissue. Stem Cells. 2009; 27:3093-102. https://doi.org/10.1002/stem.235

165. Cui X, You L, Zhu L, Wang X, Zhou Y, Li Y, et al. Change in circulating microRNA profile of obese children indicates future risk of adult diabetes. Metabol. 2018; 78:95-105. https://doi.org/10.1016/j.metabol.2017.09.006

166. Karbiener M, Pisani DF, Frontini A, Oberreiter LM, Lang E, Vegiopoulos A et al. MicroRNA-26 familyis required for human adipogenesis and drives characteristics of brown adipocytes. Stem Cells. 2014; 32:1578-90. https://doi.org/10.1002/stem.1603

167. Tang YF, Zhang Y, Li XY, Li C, Tian W, Liu L. Expression of miR-31, miR-125b-5p, and miR-326 in the adipogenic differentiation process of adipose-derived stem cells. Omics. 2009; 13:331-6. https://doi.org/10.1089/omi.2009.0017

168. Ji HL, Song CC, Li YF, He JJ, Li YL, Zheng XL, et al. MiR-125a i8nhibits porcine preadipocytes differentiation by targeting ERRα. Mol Cell Biochem. 2014; 395:155-65. https://doi.org/10.1007/s11010-014-2121-4

169. Li X. MiR-375, a microRNA related to diabetes. Gene. 2014; 533:1-4. https://doi.org/10.1016/j.gene.2013.09.105

170. Huang S, Wang S, Bian C, Yang Z, Zhou H, Zeng Y, et al. Upregulation of miR-22 promotes osteogenic differentiation and inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells by repressing HDAC6 protein expression. Stem Cells Dev. 2012; 21:2531-40. https://doi.org/10.1089/scd.2012.0014

171. Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, et al. MiR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006; 3:87-98. https://doi.org/10.1016/j.cmet.2006.01.005

172. Hsu SH, Wang B, Kota J, Yu J, Costinean S, Kutay H, et al. Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. J Clin Investig. 2012; 122:2871-83. https://doi.org/10.1172/JCI63539

173. Chen X, Liang H, Zhang J, Zen K, Zhang CT. Secreted microRNAs: A new form of intercellular communication. Trends Cell Biol. 2012; 22:125-32. https://doi.org/10.1016/j.tcb.2011.12.001

174. Cheung O, Puri P, Eicken C, Contos MJ, Mirshahi F, Maher JW, et al. Nonalcoholic steatohepatitis is associated with altered hepatic microRNA expression. Hepatol. 2008; 48:1810-20. https://doi.org/10.1002/hep.22569

175. Quaamari AE, Baroukh N, Martens GA, Lebrun P, Pipeleers D, van Obberghen E. MiR-375 targets 3ʹ1-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic β-cells. Diabetes. 2008; 57:2708-17. https://doi.org/10.2337/db07-1614

176. Lee EK, Lee MJ, Abdelmohsen K, Kim W, Kim MM, Srikantan S, et al. MiR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor expression. Mol Cell Biol. 2011; 31:626-38. https://doi.org/10.1128/MCB.00894-10

177. McCarthy JJ. The myomiR net-work in skeletal muscle plasticity. Exerc Sport Sci Rev. 2011; 39:150. https://doi.org/10.1097/JES.0b013e31821c01e1

178. Feng B, Chen S, George B, Feng Q, Chakrabarti S. MiR-133a regulates cardiomyocyte hypertrophy in diabetes. Diabetes Metab Res Rev. 2010; 26:40-49. https://doi.org/10.1002/dmrr.1054

179. Zhou Y, Gu P, Shi W, Li J, Hao Q, Cao X, et al. MicroRNA-29a induces insulin resistance by targeting PPARδ in skeletal muscle cells. Int J Mol Med. 2016; 37:931-8. https://doi.org/10.3892/ijmm.2016.2499

180. Wronska A. The role of microRNA in the development, diagnosis, and treatment of cardiovascular disease: Recent developments. J Pharmacol Exp Ther. 2023; 384:123-32. https://doi.org/10.1124/jpet.121.001152

181. Houbaviy HB, Murray MF, Sharp PA. Embryogenic stem-cell specific microRNAs. Dev Cell. 2003; 5:351-8. https://doi.org/10.1016/S1534-5807(03)00227-2

182. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol. 2004; 5(3):R13. https://doi.org/10.1186/gb-2004-5-3-r13

183. Krichevsky AM, King KS, Donahue CP, Khrapko K, Kosik KS. A microRNA array reveals extensive regulation of microRNAs during brain development. RNA. 2003; 9:1274-81. https://doi.org/10.1261/rna.5980303

184. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 2004; 101:2999-3004. https://doi.org/10.1073/pnas.0307323101

185. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of microRNA genes miR-15 and miR-16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002; 99:15524-9. https://doi.org/10.1073/pnas.242606799

186. Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, et al. MiR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer. 2008; 123:372-9. https://doi.org/10.1002/ijc.23501

187. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 2006; 103:2257-61. https://doi.org/10.1073/pnas.0510565103

188. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005; 65:6029-33. https://doi.org/10.1158/0008-5472.CAN-05-0137

189. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterol. 2007; 133:647-58. https://doi.org/10.1053/j.gastro.2007.05.022

190. Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M. MicroRNA-21 is over-expressed in pancreatic cancer and a potential predictor of survival. J Gastrointest Surg. 2008; 12(12):2171-6. https://doi.org/10.1007/s11605-008-0584-x

191. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005; 65:7065-70. https://doi.org/10.1158/0008-5472.CAN-05-1783

192. Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol. 2006; 24:4677-84. https://doi.org/10.1200/JCO.2005.05.5194

193. Mendell JT. MiRiad roles for the miR-17-92 cluster in development and disease. Cell. 2008; 133:217-22. https://doi.org/10.1016/j.cell.2008.04.001

194. Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S, et al. Identification and characterization of a novel gene, C13 or f25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res. 2004; 64:3087-95. https://doi.org/10.1158/0008-5472.CAN-03-3773

195. Hammond SM. MicroRNAs as oncogenes. Curr Opin Genet Dev. 2006; 16:4-9. https://doi.org/10.1016/j.gde.2005.12.005

196. Petrocca F, Visone R, Onrlli MR, Shah MH, Nicoloso MS, deMartino I, et al. E2F1-regulated microRNAs impair TGF-beta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008; 13:272-86. https://doi.org/10.1016/j.ccr.2008.02.013

197. Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 2005; 65:9628-32. https://doi.org/10.1158/0008-5472.CAN-05-2352

198. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005; 435:828-33. https://doi.org/10.1038/nature03552

199. Michael MZ, O'Connor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 2003; 1:882-91.

200. Metzler M, Wilda M, Busch K, Viehmann S, Borkhardt A. High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma. Genes Chromosomes Cancer. 2004; 39:167-9. https://doi.org/10.1002/gcc.10316

201. Dubey A. Computational prediction of miRNA in Gmelina arborea and their role in human metabolomics. Am J Biosci Bioeng. 2013; 1:62. https://doi.org/10.11648/j.bio.20130105.12

202. Rameshwari R. In silico prediction of miRNA in Curcuma longa and their role in human metabolomics. Int J Adv Biotechnol Res. 2013; 4(2):253-9.

203. Liang GF, Zhu YL, Sun B, Shao YH, Jing AH, Wang JH, et al. Assessing the survival of exogenous plant microRNA in mice. Food Sci Nutr. 2014; 2(4):380-8. https://doi.org/10.1002/fsn3.113

204. Zhou Z, Li X, Liu J, Dong L, Chen Q, Liu J, et al. Honeysuckle-encoded atypical microRNA-2911 directly targets influenza A viruses. Cell Res. 2015; 25(1):39-49. https://doi.org/10.1038/cr.2014.130

205. Yang Z, Cappello T, Wang L. Emerging role of microRNAs in lipid metabolism. Acta Pharm Sin B. 2015; 5:145-50. https://doi.org/10.1016/j.apsb.2015.01.002

206. Baier SR, Nguyen C, Xie F, Wood JR, Zempleni J. MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers 1-3. J Nutr Biochem Mol Genet Mech. 2014; 144(10):1495-500. https://doi.org/10.3945/jn.114.196436

207. Title AC, Denzier R, Stoffel M. Uptake and function studies of maternal milk-derived microRNAs. J Biol Chem. 2015; 290:23680-91. https://doi.org/10.1074/jbc.M115.676734

208. Pirro S, Zanella L, Kenzo M, Montesano C, Minutolo A, Potesta M, et al. MicroRNA from Moringa oleifera: Identification by high throughput sequencing and their potential contribution to plant medicinal value. PLoS One. 2016; 11(3):e0149495. https://doi.org/10.1371/journal.pone.0149495

209. Singh N, Srivastava S, Sharma A. Identification and analysis of miRNAs and their targets in ginger using bioinformatics approach. Gene. 2016; 575:570-6. https://doi.org/10.1016/j.gene.2015.09.036

210. Chin AR, Fong MY, Somlo G, Wu J, Swiderski P, Wu X, et al. Cross-kingdom inhibition of breast cancer growth by plant miR-159. Cell Res. 2016; 26(2):217-28. https://doi.org/10.1038/cr.2016.13

211. Chen X, Dai GH, Ren ZM, Tong YL, Yang F, Zhu YQ. Identification of dietetically absorbed rapeseed (Brassica campestris L.) bee pollen microRNAs in serum of mice. Biomed Res Int. 2016; 5413849. https://doi.org/10.1155/2016/5413849

212. Pastrello C, Tsay M, Mcquaid R, Abovsky M, Pasini E, Shirdel E, et al. Circulating plant miRNAs can regulate human gene expression in vitro. Sci Rep. 2016; 6:32773. https://doi.org/10.1038/srep32773

213. Liu YC, Chen WL, Kung WH, Huang HD. Plant miRNAs found in human circulating system provide evidences of cross kingdom RNAi. BMC Genom. 2017; 18(S2):112. https://doi.org/10.1186/s12864-017-3502-3

214. Kumar D, Kumar S, Ayachit G, Bhairappanavar SB, Ansari A, Sharma P, et al. Cross-kingdom regulation of putative miRNAs derived from happy tree in cancer pathway: A systems biology approach. Int J Mol Sci. 2017; 18(6):1191. https://doi.org/10.3390/ijms18061191

215. Xie W, Adolf J, Melzig MF. Identification of Viscum album L. MiRNAs and prediction of their medicinal values. PLoS One. 2017. https://doi.org/10.1371/journal.pone.0187776

216. Hou D, He F, Ma L, Cao M, Zhou Z, Wei Z, et al. The potential atheroprotective role of plant miR-156a as a repressor of monocyte recruitment on inflamed human endothelial cells. J Nutr Biochem. 2018; 57:197-205. https://doi.org/10.1016/j.jnutbio.2018.03.026

217. Patel M, Patel S, Mangukia N, Patel S, Mankad A, Pandya H, et al. Ocimum basilicum miRNOME revisited: A cross-kingdom approach. Genomics. 2019; 111(4):772-85. https://doi.org/10.1016/j.ygeno.2018.04.016

218. Gadhavi H, Patel M, Mangukia N, Shah K, Bhadresha K, Patel SK, et al. Transcriptome-wide miRNA identification of Bacopa monnieri: A cross-kingdom approach. Plant Signal Behav. 2020; 15:1699265. https://doi.org/10.1080/15592324.2019.1699265

219. Shatsberg Z, Zhang X, Ofek P, Malhotra S, Krivitsky A, Scomparin A, et al. Functionalized nanogels carrying an anticancer microRNA for glioblastoma therapy. J Control Rel. 2016; 239:159-68. https://doi.org/10.1016/j.jconrel.2016.08.029

220. Collison A, Mattes J, Plank M, Foster PS. Inhibition of house dust mite-induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment. J Allergy Clin Immunol. 2011; 128(1):160-7. https://doi.org/10.1016/j.jaci.2011.04.005

221. Yang YP, Chien Y, Chiou GY, Cherng JY, Wang ML, Lo WL, et al. Inhibition of cancer stem cell-like properties and reduced chemo-radio-resistance of glioblastoma using microRNA-145 with cationic polyurethane-short branch PEI. Biomater. 2012; 33(5):1462-76. https://doi.org/10.1016/j.biomaterials.2011.10.071

222. Plank MW, Maltby S, Tay HL, Stewart J, Eyers F, Hansbro PM, et al. MicroRNA expression is altered in an ovalbumin-induced asthma model and targeting miR-155 with antago-miRs reveals cellular specificity. PLoS One. 2015; 10(12):e0144810. https://doi.org/10.1371/journal.pone.0144810

223. Kim RY, Horvat JC, Pinkerton JW, Starkey MR, Essilfie AT, Mayall JR, et al. MicroRNA-21 drives severe steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase-mediated suppression of histone deacetylase 2. J Allergy Clin Immunol. 2017; 139(2):519-32. https://doi.org/10.1016/j.jaci.2016.04.038

224. Tan X, Kim G, Lee D, Oh J, Kim M, Piao C, et al. A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense-oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model. Biomater Sci. 2018; 6(2):407-17. https://doi.org/10.1039/C7BM01088E

225. Zhang Y, Kollmer M, Buhrman JS, Tang MY, Gemeinhart RA. Arginine-rich cell penetrating peptide-anti-microRNA complexes decrease glioblastoma migration potential. Peptides. 2014; 58:83-90. https://doi.org/10.1016/j.peptides.2014.06.008

226. Kucukturkmen B, Devrim B, Saka OM, Yilmaz S, Arsoy T, Bozkir A. Co-delivery of pemetrexed and miR-21 antisense oligonucleotide by lipid-polymer hybrid nanoparticles and effects on glioblastoma cells. Drug Dev Ind Pharm. 2017; 43(1):12-21. https://doi.org/10.1080/03639045.2016.1200069

227. Kucukturkmen B, Bozkir A. Development and characterization of cationic solid lipid nanoparticles for co-delivery of pemetrexed and miR-21 antisense oligonucleotide to glioblastoma cells. Drug Dev Ind Pharm. 2018; 44(2):306-15. https://doi.org/10.1080/03639045.2017.1391835

228. Sukumar UK, Bose RJ, Malhotra M, Babikir HA, Afjei R, Robinson E, et al. Intranasal delivery of targeted polyfunctional gold-iron oxide nanoparticles loaded with therapeutic microRNAs for combined theranostic multimodality imaging and presensitization of glioblastoma to temozolomide. Biomater. 2019; 218:119342. https://doi.org/10.1016/j.biomaterials.2019.119342

229. Costa PM, Cardoso AL, Custodia C, Cunha P, de Almeida LP, de Lima MCP. MiRNA-21 silencing mediated by tumor-targeted nanoparticles combined with sunitinib: A new multimodal gene therapy approach for glioblastoma. J Control Rel. 2015; 207:31-9. https://doi.org/10.1016/j.jconrel.2015.04.002

230. Zhang Y, Buhrman JS, Liu Y, Rayahin JE, Gemeinhart RA. Reducible micelleplexes are stable systems for anti-miRNA delivery in cerebrospinal fluid. Mol Pharm. 2016; 13(6):1791-9. https://doi.org/10.1021/acs.molpharmaceut.5b00933

231. Lee TJ, Yoo JY, Shu D, Li H, Zhang J, Yu JG, et al. RNA nanoparticle-based targeted therapy for glioblastoma through inhibition of oncogenic miR-21. Mol Ther. 2017; 25(7):1544-55. https://doi.org/10.1016/j.ymthe.2016.11.016

232. Griveau A, Bejaud J, Anthiya S, Avril S, Autret D, Garcion E. Silencing of miR-21 by locked nucleic acid-lipid nanocapsule complexes sensitize human glioblastoma cell to radiation-induced cell-death. Int J Pharm. 2013; 454(2):765-74. https://doi.org/10.1016/j.ijpharm.2013.05.049

233. Qian X, Long L, Shi Z, Liu C, Qiu M, Sheng J, et al. Star-branched amphiphilic PLA-b-PDMAEMA copolymers for co-delivery of miR-21 inhibitor and doxorubicin to treat glioma. Biomater. 2014; 35(7):2322-35. https://doi.org/10.1016/j.biomaterials.2013.11.039

234. Zhao Y, Cui X, Zhu W, Chen X, Shen C, Liu Z, et al. Synergistic regulatory effects of microRNAs on brain glioma cells. Mol Med Rep. 2017; 16(2):1409-16. https://doi.org/10.3892/mmr.2017.6709

235. Kim G, Kim M, Lee Y, Byun JW, Lee M. Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using 17-peptide decorated exosomes. J Control Rel. 2020; 317:273-81. https://doi.org/10.1016/j.jconrel.2019.11.009

236. Li JJ, Tay HL, Maltby S, Xiang Y, Eyers F, Hatchwell L, et al. MicroRNA-9 regulates steroid-resistant airway hyper responsiveness by reducing protein phosphatase 2A activity. J Allergy Clin Immunol. 2015; 136(2):462-73. https://doi.org/10.1016/j.jaci.2014.11.044

237. Munoz JL, Bliss SA, Greco SJ, Ramkissoon SH, Ligon KL, Rameshwar P. Delivery of functional anti-miR-9 by mesenchymal stem cell-derived exosomes to glioblastoma multiforme cells conferred chemosensitivity. Mol Ther Nucl Acids. 2013; 2:e126. https://doi.org/10.1038/mtna.2013.60

238. Baker JR, Vuppusetty C, Colley T, Hassibi S, Fenwick PS, Donnelly LE, et al. MicroRNA-570 is a novel regulator of cellular senescence and inflammaging. FASEB J. 2019; 33(2):1605-16. https://doi.org/10.1096/fj.201800965R

239. Hsu ACY, Parsons K, Moheimani F, Knight DA, Hansbro PM, Fujita T, et al. Impaired antiviral stress granule and IFN-β enhanceosome formation enhances susceptibility to influenza infection in chronic obstructive pulmonary disease epithelium. Am J Respir Cell Mol Biol. 2016; 55(1):117-27. https://doi.org/10.1165/rcmb.2015-0306OC

240. Hsu ACY, Dua K, Starkey MR, Haw TJ, Nair PM, Nichol K, et al. MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD. JCI Insight. 2017; 2(7):e90443. https://doi.org/10.1172/jci.insight.90443

241. He S, Li Z, Yu Y, Zeng Q, Cheng Y, Ji W, et al. Exosomal miR-499a-5p promotes cell proliferation, migration and EMT via mTOR signaling pathway in lung adenocarcinoma. Exp cell Res. 2019; 379(2):203-13. https://doi.org/10.1016/j.yexcr.2019.03.035

242. Wang JX, Jiao JQ, Li Q, Long B, Wang K, Liu JP, et al. MiR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1. Nat Med. 2011; 17(1):71-8. https://doi.org/10.1038/nm.2282

243. Cha ST, Chen PS, Johansson G, Chu CY, Wang MY, Jeng YM, et al. MicroRNA-519c suppresses hypoxia-inducible factor-1αexpression and tumor angiogenesis. Cancer Res. 2010; 70(7):2675-85. https://doi.org/10.1158/0008-5472.CAN-09-2448

244. Lin CW, Chang YL, Chang YC, Lin JC, Chen CC, Pan SH, et al. MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1. Nat Commun. 2013; 4:1877. https://doi.org/10.1038/ncomms2876

245. Mao G, Liu Y, Fang X, Liu Y, Fang L, Lin L, et al. Tumor-derived microRNA-494 promotes angiogenesis in non-small cell lung cancer. Angiogenesis. 2015; 18(3):373-82. https://doi.org/10.1007/s10456-015-9474-5

246. Shi Y, Liu C, Liu X, Tang DG, Wang J. The microRNA miR-34a inhibits non-small cell lung cancer (NSCLC) growth and the CD44 hi stem-like NSCLC cells. PLoS One. 2014; 9(3):e90022. https://doi.org/10.1371/journal.pone.0090022

247. Ofek P, Calderon M, Mehrabadl FS, Krivitsky A, Ferber S, Tiram G, et al. Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a poly-glycerol-based polyplex. Nanomed. 2016; 12(7):2201-14. https://doi.org/10.1016/j.nano.2016.05.016

248. Sun B, Yang N, Jiang Y, Zhang H, Hou C, Ji C, et al. AntagomiR-1290 suppresses CD133+ cells in non-small cell lung cancer by targeting fyn-related Src family tyrosine kinase. Tumor Biol. 2015; 36(8):6223030. https://doi.org/10.1007/s13277-015-3307-4

249. Wu L, Pu X, Wang Q, Cao J, Xu F, Xu LI, et al. MiR-96 induces cisplatin chemoresistance in non-small cell lung cancer cells by down-regulating SAMD9. Oncol Lett. 2016; 11(2):945-52. https://doi.org/10.3892/ol.2015.4000

250. Sun CC, Li SJ, Yuan ZP, Li DJ. MicroRNA-346 facilitates cell growth and metastasis, and suppresses cell apoptosis in human non-small cell lung cancer by regulation of XPC/ERK/Snail/E-cadherin pathway. Aging (Albany, NY). 2016; 8(10):2509-24. https://doi.org/10.18632/aging.101080

251. Zhang Y, Li M, Hu C. Exosomal transfer of miR-214 mediates gefitinib resistance in non-small cell lung cancer. Biochem Biophys Res Commun. 2018; 507(1-4):457-64. https://doi.org/10.1016/j.bbrc.2018.11.061

252. Ge L, Habiel DM, Hansbro PM, Kim RY, Gharib SA, Edelman JD, et al. MiR-323a-3p regulates lung fibrosis by targeting multiple profibrotic pathways. JCI Insight. 2016; 1(20):e90301. https://doi.org/10.1172/jci.insight.90301

253. Bhattacharyya S, Balakathiresan NS, Dalgard C, Gutti U, Armistead D, Jozwik C, et al. Elevated miR-155 promotes inflammation in cystic fibrosis by driving hyper expression of interleukin-8. J Biol Chem. 2011; 286(13):11604-15. https://doi.org/10.1074/jbc.M110.198390

254. Potus F, Malenfant S, Graydon C, Mainguy V, Tremblay E, Breuils-Bonnet S, et al. Impaired angiogenesis and peripheral muscle microcirculation loss contribute to exercise intolerance in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2014; 190(3):318-28. https://doi.org/10.1164/rccm.201402-0383OC

255. Pullamsetti SS, Doebele C, Fischer A, Savai R, Kojonazarov B, Dahal BK, et al. Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension. Am J Respir Crit Care Med. 2012; 185(4):409-19. https://doi.org/10.1164/rccm.201106-1093OC

256. Sharma S, Umar S, Centala A, Eghbali M. Role of miR-206 in genistein-induced rescue of pulmonary hypertension in monocrotaline model. J Appl Physiol. 2015; 119(12):1374-82. https://doi.org/10.1152/japplphysiol.00699.2014

257. Liu X, Li G, Su Z, Jiang Z, Chen L, Wang J, et al. Poly (amido amine) is an ideal carrier of miR-7 for enhancing gene silencing effects on the EGFR pathway in U251 glioma cells. Oncol Rep. 2013; 29(4):1387-94. https://doi.org/10.3892/or.2013.2283

258. Wang W, Dai LX, Zhang S, Yang Y, Yan N, Fan P, et al. Regulation of epidermal growth factor receptor signaling by plasmid-based microRNA-7 inhibits human malignant gliomas growth and metastasis in vivo. Neoplasma. 2013; 60(3):274-83. https://doi.org/10.4149/neo_2013_036

259. Liang C, Sun W, He H, Zhang B, Ling C, Wang B, et al. Antitumor effect of a new nano-vector with miRNA-135a on malignant glioma. Int J Nanomed. 2018; 13:209. https://doi.org/10.2147/IJN.S148142

260. Katakowski M, Buller B, Zheng X, Lu Y, Rogers T, Osobamiro O, et al. Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett. 2013; 335(1):201-4. https://doi.org/10.1016/j.canlet.2013.02.019

261. Lang FM, Hossain A, Gumin J, Momin EN, Shimizu Y, Ledbetter D, et al. Mesenchymal stem cells as natural biofactories for exosomes carrying miR-124a in the treatment of gliomas. Neuro Oncol. 2018; 20(3):380-90. https://doi.org/10.1093/neuonc/nox152

262. Suzhi Z, Liang T, Yuexia P, Lucy L, Xiaoting H, Yuan Z, et al. Gap junctions enhance the antiproliferative effect of microRNA-124-3p in glioblastoma cells. J Cell Physiol. 2015; 230(10):2476-88. https://doi.org/10.1002/jcp.24982

263. Lee HK, Finmiss S, Cazacu S, Bucris E, Ziv-Av A, Xiang C, et al. Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal. Oncotarget. 2013; 4(2):346. https://doi.org/10.18632/oncotarget.868

264. Fang DZ, Wang YP, Liu J, Hui XB, Wang XD, Chen X, et al. MicroRNA-129-3p suppresses tumor growth by targeting E2F5 in glioblastoma. Eur Rev Med Pharmacol Sci. 2018; 22(4):1044-50.

265. He Z, Ruan X, Liu X, Zheng J, Liu Y, Liu L, et al. FUS/circ_002136/miR-138-5p/SOX13 feedback loop regulates angiogenesis in glioma. J Exp Clin Cancer Res. 2019; 38(1):1-19. https://doi.org/10.1186/s13046-019-1065-7

266. Wang L, Shi ZM, Jiang CF, Liu X, Chen QD, Qian X, et al. MiR-143 acts as a tumor suppressor by targeting N-ras and enhances temozolomide-induced apoptosis in glioma. Oncotarget. 2014; 5(14):5416. https://doi.org/10.18632/oncotarget.2116

267. Zhang X, Yu J, Zhao C, Ren H, Yuan Z, Zhang B, et al. MiR-181b-5p modulates chemosensitivity of glioma cells to temozolomide by targeting Bcl-2. Biomed Pharmacother. 2019; 109:2192-202. https://doi.org/10.1016/j.biopha.2018.11.074

268. Wang XF, Shi ZM, Wang XR, Cao L, Wang YY, Zhang JX, et al. MiR-181d acts as a tumor suppressor in glioma by targeting K-ras and Bcl-2. J Cancer Res Clin Oncol. 2012; 138(4):573-84. https://doi.org/10.1007/s00432-011-1114-x

269. Kouri FM, Hurley LA, Daniel WL, Day ES, Hua Y, Hao L, et al. MiR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma. Genes Dev. 2015; 29(7):732-45. https://doi.org/10.1101/gad.257394.114

270. Jana A, Narula P, Chugh A, Kulshreshtha R. Efficient delivery of anti-miR-210 using tachyplesin, a cell penetrating peptide, for glioblastoma treatment. Int J Pharm. 2019; 572:118789. https://doi.org/10.1016/j.ijpharm.2019.118789

271. Fan L, Yang Q, Tan J, Qiao Y, Wang Q, He J, et al. Dual loading miR-218 mimics and temozolomide using AuCOOH@FA-CS drug delivery system: Promising targeted anti-tumor drug delivery system with sequential release functions. J Exp Clin Cancer Res. 2015; 34(1):1-9. https://doi.org/10.1186/s13046-015-0216-8

272. Fareh M, Alamirac F, Turchi L, Burel-Vandenbos F, Paquis P, Fontaine D, et al. Cell-based therapy using miR-302-367 expressing cells represses glioblastoma growth. Cell Death Dis. 2017; 8(3):e2713. https://doi.org/10.1038/cddis.2017.117

273. Bertucci A, Prasetyanto EA, Septiadi D, Manicardi A, Brognara E, Gambari R, et al. Combined delivery of temozolomide and anti-miR-221PNA using mesoporous silica nanoparticles induces apoptosis in resistant glioma cells. Small. 2015; 11(42):5687-95. https://doi.org/10.1002/smll.201500540

274. Brognara E, Fabbri E, Montagner G, Gasparello J, Manicardi A, Corradini R, et al. High levels of apoptosis are induced in human glioma cell lines by co-administration of peptide nucleic acids targeting miR-221 and miR-222. Int J Oncol. 2016; 48(3):1029-38. https://doi.org/10.3892/ijo.2015.3308

275. Yin PT, Shah BP, Lee KB. Combined magnetic nanoparticle-based microRNA and hyperthermia therapy to enhance apoptosis in brain cancer cells. Small. 2014; 10(20):4106-12. https://doi.org/10.1002/smll.201400963

276. Yang HW, Huang CY, Lin CW, Liu HL, Huang CW, Liao SS, et al. Gadolinium-functionalized nanographene oxide for combined drug and microRNA delivery and magnetic resonance imaging. Biomater. 2014; 35(24):6534-42. https://doi.org/10.1016/j.biomaterials.2014.04.057

277. Esposito CL, Nuzzo S, Kumar SA, Rienzo A, Lawrence CL, Pallini R, et al. A combined microRNA-based targeted therapeutic approach to eradicate glioblastoma stem-like cells. J Control Rel. 2016; 238:43-57. https://doi.org/10.1016/j.jconrel.2016.07.032

278. Lopez-Bertoni H, Kozielski KL, Rui Y, Lal B, Vaughan H, Wilson DR, et al. Bio-reducible polymeric nanoparticles containing multiplexed cancer stem cell regulating miRNAs inhibit glioblastoma growth and prolong survival. Nano Lett. 2018; 18(7):4086-94. https://doi.org/10.1021/acs.nanolett.8b00390

279. Yue X, Wang P, Xu J, Zhu Y, Sun G, Pang Q, et al. MicroRNA-205 functions as a tumor suppressor in human glioblastoma cells by targeting VEGF-A. Oncol Rep. 2012; 27(4):1200-06. https://doi.org/10.3892/or.2011.1588

280. Esau CC, Monia BP. Therapeutic potential for microRNAs. Adv Drug Deliv Rev. 2007; 59:101-14. https://doi.org/10.1016/j.addr.2007.03.007

281. Li Z, Rana TM. Therapeutic targeting of microRNAs: Current status and future challenges. Nat Rev Drug Discov. 2014; 13:622-38. https://doi.org/10.1038/nrd4359

282. Bader AG, Brown D, Winkler M. The promise of microRNA replacement therapy. Cancer Res. 2010; 70:7027-30. https://doi.org/10.1158/0008-5472.CAN-10-2010

283. Banales JM, Saez E, Uriz M, Sarvide S, Urribarri AD, Splinter P, et al. Up-regulation of microRNA 506 leads to decreased Cl-/HCO3- anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis. Hepatol. 2012; 56:687-97. https://doi.org/10.1002/hep.25691

284. Gambari R, Brognara E, Spandidos DA, Fabbri E. Targeting onco-miRNAs and mimicking tumor suppressor miRNAs: New trends in the development of miRNA therapeutic strategies in oncology. Int J Oncol. 2016; 49:5-32. https://doi.org/10.3892/ijo.2016.3503

285. Cheng CJ, Bahal R, Babar IA, Pincus Z, Barrera F, Liu C, et al. MicroRNA silencing for cancer therapy targeted to the tumor microenvironment. Nature. 2015; 518:107-10. https://doi.org/10.1038/nature13905

286. Tang L, Chen HY, Hao NB, Tang B, Guo H, Yong X, et al. MicroRNA inhibitors: Natural and artificial sequestration of microRNA. Cancer Lett. 2017; 407:139-47. https://doi.org/10.1016/j.canlet.2017.05.025

287. Bravo V, Rosero S, Ricordi C, Pastori RL. Instability of miRNA and cDNAs derivatives in RNA preparations. Biochem Biophys Res Commun. 2007; 353:1052-55. https://doi.org/10.1016/j.bbrc.2006.12.135

288. Cho WC. Role of miRNAs in lung cancer. Expert Rev Mol Diagn. 2009; 9:773-6. https://doi.org/10.1586/erm.09.57

289. Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, et al. Fatality in mice due to over-saturation of cellular microRNA / short hairpin RNA pathways. Nature. 2006; 441:537-41. https://doi.org/10.1038/nature04791

290. Pecot CV, Calin GA, Coleman RL, Lopez-Berestein G, Sood AK. RNA interference in the clinic: Challenges and future directions. Nat Rev Cancer. 2011; 11:59-67. https://doi.org/10.1038/nrc2966

291. Wang H, Jiang Y, Peng H, Chen Y, Zhu P, Huang Y. Recent progress in microRNA delivery for cancer therapy by non-viral synthetic vectors. Adv Drug Deliv Rev. 2015; 81:142-60. https://doi.org/10.1016/j.addr.2014.10.031

292. Crooke ST, Graham MJ, Zuckerman JE, Brooks D, Conklin BS, Cummins LL, et al. Pharmacokinetic properties of several novel oligonuclotide analogs in mice. J Pharmacol Exp Ther. 1996; 277(2):923-37. https://doi.org/10.1016/S0022-3565(25)12951-0

293. Van Rooij E, Kauppinen S. Development of microRNA therapeutics is coming of age. EMBO Mol Med. 2014; 6:851-64. https://doi.org/10.15252/emmm.201100899

294. Wahlestedt C, Salmi P, Good L, Kela J, Johnsson T, Hokfelt T, et al. Potent and nontoxic antisense oligonucleotides containing locked nucleic acids. Proc Natl Acad Sci USA. 2000; 97:5633-8. https://doi.org/10.1073/pnas.97.10.5633

295. Sun X, Guo Q, Wei W, Robertson S, Yuan Y, Luo X. Current progress on microRNA-based gene delivery in the treatment of osteoporosis and osteoporotic fracture. Int J Endocrinol. 2019; 2019:6782653. https://doi.org/10.1155/2019/6782653

296. Chen Y, Gao DY, Huang L. In vivo delivery of miRNAs for cancer therapy: Challenges and strategies. Adv Drug Deliv Rev. 2015; 81:128-41. https://doi.org/10.1016/j.addr.2014.05.009

297. Forterre A, Komuro H, Aminova S, Harada M. A comprehensive review of cancer microRNA therapeutic delivery strategies. Cancers. 2020; 12:1852. https://doi.org/10.3390/cancers12071852

298. Liu CG, Song J, Zhang YQ, Wang PC. MicroRNA-193b is a regulator of amyloid precursor in the blood and cerebrospinal fluid derived exosomal microRNA-193b is a biomarker of Alzheimer's disease. Mol Med Rep. 2014; 10:2395-400. https://doi.org/10.3892/mmr.2014.2484

299. Trang P, Medina PP, Wiggins JF, Ruffino L, Lelnar K, Omotola M, et al. Regression of murine lung tumors by the let-7 microRNA. Oncogene. 2010; 29:1580-7. https://doi.org/10.1038/onc.2009.445

300. Theis T, Yoo M, Park CS, Chen J, Kugler S, Gibbs KM, et al. Lentiviral delivery of miR-133b improves functional recovery after spinal cord injury in mice. Mol Neurobiol. 2017; 54:4659-71. https://doi.org/10.1007/s12035-016-0007-z

301. Yin L, Leeler GD, Zhang Y, Hoffman BE, Ling C, Qing K, et al. AAV3-miRNA vectors for growth suppression of human hepatocellular carcinoma cells in vitro and human liver tumors in a murine xenograft model in vivo. Gene Ther. 2020; 28(7-8):422-34. https://doi.org/10.1038/s41434-020-0140-1

302. Martier R, Sogorb-Gonzalex M, Stricker-Shaver J, Hubener-Schmid J, Keskin S, Klima J, et al. Development of an AAV-based microRNA gene therapy to treat Machado-Joseph disease. Mol Ther Methods Clin Dev. 2019; 15:343-58. https://doi.org/10.1016/j.omtm.2019.10.008

303. Pourshafie N, Lee PR, Chen KL, Harmison GG, Bott LC, Fischbeck KH, et al. Systemic delivery of microRNA using recombinant adeno-associated virus serotype-9 to treat neuromuscular diseases in rodents. J Vis Exp. 2018; 138:55724. https://doi.org/10.3791/55724-v

304. Liu XL, Pan Q, Cao HX, Xin FZ, Zhao ZH, Yang RX, et al. Lipotoxic hepatocyte-derived exosomal microRNA-192-5p activates macrophages through Rictor/Akt/Forkhead Box transcription factor O1 signaling in nonalcoholic fatty liver disease. Hepatol. 2020; 72:454-69. https://doi.org/10.1002/hep.31050

305. Bose RJC, Uday Kumar S, Zeng Y, Afjei R, Robinson E, Lau K, et al. Tumor cell-derived extracellular vesicle-coated nanocarriers: An efficient theranostic platform for the cancer-specific delivery of anti-miR-21 and imaging agents. ACS Nano. 2018; 12(11):10817-32. https://doi.org/10.1021/acsnano.8b02587

306. Kobayashi M, Sawada K, Miyamoto M, Shimizu A, Yamamoto M, Kinose Y, et al. Exploring the potential of engineered exosomes as delivery systems for tumor-suppressor microRNA replacement therapy in ovarian cancer. Biochem Biophys Res Commun. 2020; 527:153-61. https://doi.org/10.1016/j.bbrc.2020.04.076

307. Ohno S, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyana N, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013; 21:185-91. https://doi.org/10.1038/mt.2012.180

308. Lou G, Song X, Yang F, Wu S, Wang J, Chen Z, et al. Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol. 2015; 8:122. https://doi.org/10.1186/s13045-015-0220-7

309. Vazquez-Rios AJ, Molina-Crespo A, Bouzo BL, Lopez-Lopez R, Moreno-Bueno G, de la Fuente M. Exosome-mimetic nanoplatforms for targeted cancer drug delivery. J Nanobiotechnol. 2019; 17:85. https://doi.org/10.1186/s12951-019-0517-8

310. Trajkovski M, Hausser J, Soutschek J, Bhat B, Akin A, Zavolan M, et al. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature. 2011; 474:649-53. https://doi.org/10.1038/nature10112

311. Yang J, Brown ME, Zhang H, Martinez M, Zhao Z, Bhutani S, et al. High-throughput screening identifies microRNAs that target Nox2 and improve function after acute myocardial infarction. Am J Physiol Heart Circ Physiol. 2017; 312:H1002-12. https://doi.org/10.1152/ajpheart.00685.2016

312. Kheirolomoom A, Kim CW, Seo JW, Kumar S, Son DJ, Gagnon MKJ, et al. Multifunctional nanoparticles facilitate molecular targeting and miRNA delivery to inhibit atherosclerosis in Apo E-1-mice. ACS Nano. 2015; 9:8885-97. https://doi.org/10.1021/acsnano.5b02611

313. Akinc A, Querbes W, De S, Qin J, Frank-Kamenetsky M, Jayaprakash KN, et al. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol Ther. 2010; 18:1357-64. https://doi.org/10.1038/mt.2010.85

314. Misso G, Di Martino MT, De Rosa G, Farooqi AA, Lombardi A, Campani V, et al. MiR-34: A new weapon against cancer? Mol Ther Nucleic Acids. 2014; 3:e194. https://doi.org/10.1038/mtna.2014.47

315. Rai K, Takigawa N, Ito S, Kashihara H, Ichihara E, Yasuda T, et al. Liposomal delivery of microRNA-7-expressing plasmid overcomes epidermal growth factor tyrosine kinase inhibitor-resistance in lung cancer cells. Mol Cancer Ther. 2011; 10:1720-7. https://doi.org/10.1158/1535-7163.MCT-11-0220

316. Wu Y, Crawford M, Mao Y, Lee RJ, Davis IC, Elton TS, et al. Therapeutic delivery of microRNA-29b cationic lipoplexus for lung cancer. Mol Ther Nucleic Acids. 2013; 2:e84. https://doi.org/10.1038/mtna.2013.14

317. Cortez MA, Valdocanas D, Zhang X, Zhan Y, Bhardwaj V, Calin GA, et al. Therapeutic delivery of miR-200c enhances radiosensitivity in lung cancer. Mol Ther. 2014; 22(8):1494-503. https://doi.org/10.1038/mt.2014.79

318. Gokita K, Inoue J, Ishihara H, Kojima K, Inazawa J. Therapeutic potential of LNP-mediated delivery of miR-634 for cancer therapy. Mol Ther Nucleic Acids. 2020; 19:330-8. https://doi.org/10.1016/j.omtn.2019.10.045

319. De Antonellis P, Liguori L, Falanga A, Carotenuto M, Ferrucci V, Andolfo I, et al. MicroRNA 199b-5p delivery through stable nucleic acid lipid particles (SNALPs) in tumorigenic cell lines. Naunyn Schmiedebergs Arch Pharmacol. 2013; 386:287-302. https://doi.org/10.1007/s00210-013-0837-4

320. Yin H, Wang H, Li Z, Shu D, Guo P. RNA micelles for the systemic delivery of anti-miRNA for cancer targeting and inhibition without ligand. ACS Nano. 2019; 13(1):706-17. https://doi.org/10.1021/acsnano.8b07948

321. Shu D, Li H, Shu Y, Xiong G, Carson III WE, Haque F, et al. Systemic delivery of anti-miRNA for suppression of triple negative breast cancer utilizing RNA nanotechnology. ACS Nano. 2015; 9(10):9731-40. https://doi.org/10.1021/acsnano.5b02471

322. Su J, Baigude H, Mc Carroll J, Rana TM. Silencing microRNA by interfering nanoparticles in mice. Nucleic Acids Res. 2011; 39(6):e38. https://doi.org/10.1093/nar/gkq1307

323. Li Y, Duo Y, Bi J, Zeng X, Mei L, Bao S, et al. Targeted delivery of anti-miR-155 by functionalized mesoporous silica nanoparticles for colorectal cancer therapy. Int J Nanomed. 2018;13:1241-56. https://doi.org/10.2147/IJN.S158290

324. Jin H, Yu Y, Chrisler WB, Xiong Y, Hu D, Lei C. Delivery of microRNA-10b with polylysine nanoparticles for inhibition of breast cancer cell wound healing. Breast Cancer (Auckl). 2012; 6:9-19. https://doi.org/10.4137/BCBCR.S8513

325. Cheng CJ, Saltzman WM. Polymer nanoparticle-mediated delivery of microRNA inhibition and alternative splicing. Mol Pharm. 2012; 9(5):1481-8. https://doi.org/10.1021/mp300081s

326. Liu XQ, Song WJ, Sun TM, Wang J. Targeted delivery of antisense inhibitor of miRNA for anti-angiogenesis therapy using cRGD-functionalized nanoparticles. Mol Pharm. 2011;8(1):250-9. https://doi.org/10.1021/mp100315q

327. Di Mauro V, Iafisco M, Salvarani N, Vacchiano M, Carullo P, Ramirez-Rodriguez GB, et al. Bioinspired negatively charged calcium phosphate nanocarriers for cardiac delivery of microRNAs. Nanomed. 2016; 11:891-906. https://doi.org/10.2217/nnm.16.26

328. Hiraki M, Nishimura J, Takahashi H, Wu X, Takahashi Y, Miyo M, et al. Concurrent targeting of KRAS and AKT by miR-4689 is a novel treatment against mutant KRAS colorectal cancer. Mol Ther Nucleic Acids. 2015; 4:e231. https://doi.org/10.1038/mtna.2015.5

329. Inoue A, Mizushima T, Wu X, Okuzaki D, Kambara N, Ishikawa S, et al. A miR-29b byproduct sequence exhibits potent tumor-suppressive activities via inhibition of NF-kappaB signaling in KRAS-mutant colon cancer cells. Mol Cancer Ther. 2018; 17:977-87. https://doi.org/10.1158/1535-7163.MCT-17-0850

330. Babar IA, Cheng CJ, Booth CJ, Liang X, Weidhaas JB, Saltzman WM, et al. Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma. Proc Natl Acad Sci USA. 2012; 109(26):E1695-704. https://doi.org/10.1073/pnas.1201516109

331. Ren Y, Kang CS, Yuan XB, Zhou X, Xu P, Han L, et al. Co-delivery of as-miR-21 and 5-FU by poly (amidoamine) dendrimer attenuates human glioma cell growth in vitro. J Biomater Sci Polym Ed. 2010; 21(3):303-14. https://doi.org/10.1163/156856209X415828

332. Devulapally R, Sekar NM, Sekar TV, Foygel K, Massoud TF, Willmann JK, et al. Polymer nanoparticles mediated codelivery of anti-miR-10b and anti-miR-21 for achieving triple negative breast cancer therapy. ACS Nano. 2015; 9(3):2290-302. https://doi.org/10.1021/nn507465d

333. Ibrahim AF, Weirauch U, Thomas M, Grunweller A, Hartmann RK, Aigner A. MicroRNA replacement therapy for miR-145 and miR-33a is efficacious in a model of colon carcinoma. Cancer Res. 2011; 71:5214-24. https://doi.org/10.1158/0008-5472.CAN-10-4645

334. Hu Q, Wang K, Sun X, Li Y, Fu Q, Liang T, et al. A redox-sensitive, oligopeptide-guided, self-assembling, and efficiency-enhanced (ROSE) system for functional delivery of microRNA therapeutics for treatment of hepatocellular carcinoma. Biomater. 2016; 104:192-200. https://doi.org/10.1016/j.biomaterials.2016.07.016

335. Seo YE, Suh HW, Bahal R, Josowitz A, Zhang J, Song E, et al. Nanoparticle-mediated intratumoral inhibition of miR-21 for improved survival in glioblastoma. Biomater. 2019; 201:87-98. https://doi.org/10.1016/j.biomaterials.2019.02.016

336. Nguben MA, Wyatt H, Susser L, Geoffrion M, Rasheed A, Duchez AC, et al. Delivery of microRNAs by chitosan nanoparticles to functionally alter macrophage cholesterol efflux in vitro and in vivo. ACS Nano. 2019; 13:6491-505. https://doi.org/10.1021/acsnano.8b09679

337. Ouimet M, Ediriweera HN, Gundra UM, Sheedy FJ, Ramkhelawon B, Hutchison SB, et al. MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis. J Clin Investig. 2015; 125:4334-48. https://doi.org/10.1172/JCI81676

338. Yang H, Qin X, Wang H, Zhao X, Liu Y, Wo HT, et al. An in vivo miRNA delivery system for restoring infracted myocardium. ACS Nano. 2019; 13:9880-94. https://doi.org/10.1021/acsnano.9b03343

339. Bejerano T, Etzion S, Elyagon S, Etzion Y, Cohen S. Nanoparticle delivery of miRNA-21 mimic to cardiac macrophages improves myocardial remodeling after myocardial infarction. Nano Lett. 2018; 18:5885-91. https://doi.org/10.1021/acs.nanolett.8b02578

340. Yotsumoto F, Oki E, Tokunaga E, Maehara Y, Kuroki M, Miyamoto S. HB-EGF orchestrates the complex signals involved in triple-negative and trastuzumab-resistant breast cancer. Int J Cancer. 2010; 127:2707-17. https://doi.org/10.1002/ijc.25472

341. Wang HX, Xiong MH, Wang YC, Zhu J, Wang J. N-acetylgalactosamine functionalized mixed micellar nanoparticles for targeted delivery of siRNA to liver. J Control Rel. 2013; 166:106-14. https://doi.org/10.1016/j.jconrel.2012.12.017

342. Dhuri K, Bechtold C, Quijano E, Pham H, Gupta A, Vikram A, et al. Antisense oligonucleotides: An emerging area in drug discovery and development. J Clin Med. 2020; 9:1-24. https://doi.org/10.3390/jcm9062004

343. Jiao LR, Frampton AE, Jacob J, Pellegrino L, Krell J, Giamas G, et al. MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors. PLoS One. 2012; 7:e32068. https://doi.org/10.1371/journal.pone.0032068

344. Iacomino G. MiRNAs: The road from bench to bedside. Genes. 2023; 14:314. https://doi.org/10.3390/genes14020314

345. Nan Y, Zhang YJ. Antisense phosphorodiamidate morpholino oligomers as novel antiviral compounds. Front Microbiol. 2018; 9:750. https://doi.org/10.3389/fmicb.2018.00750

346. Jopling CL, Schutz S, Sarnow P. Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis c virus RNA genome. Cell Host Microbe. 2008; 4:77-85. https://doi.org/10.1016/j.chom.2008.05.013

347. Lindow M, Kauppinen S. Discovering the first microRNA-targeted drug. J Cell Biol. 2012; 199:407-12. https://doi.org/10.1083/jcb.201208082

348. Dasgupta I, Chatterjee A. Recent advances in miRNA delivery systems. Methods Protoc. 2021; 4:10. https://doi.org/10.3390/mps4010010

349. Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk MF, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis c virus infection. Science. 2010; 327(5962):198-201. https://doi.org/10.1126/science.1178178

350. Brasch DA, Corey DR. Novel antisense and peptide nucleic acid strategies for controlling gene expression. Biochem. 2002; 41:4503-10. https://doi.org/10.1021/bi0122112

351. Ploumaki I, Triantafyllou E, Koumprentziotis IA, Karampinos K, Drougkas K, Karavolias I, et al. Bcl-2 pathway inhibition in solid tumors: A review of clinical trials. Clinic Translat Oncol. 2023; 25:1554-78. https://doi.org/10.1007/s12094-022-03070-9

352. Keskin S, Brouwers CC, Sogorb-Gonzalez M, Martier R, Depla JA, Valles A, et al. AAV5-miHTT lowers Huntingtin mRNA and protein without off-target effects in patient-derived neuronal cultures and astrocytes. Mol Ther Methods Clin Dev. 2019; 15:275-84. https://doi.org/10.1016/j.omtm.2019.09.010

353. Miniarikova J, Zanella I, Huseinovic A, van der Zon T, Hanemaaijer E, Martier R, et al. Design, characterization, and lead selection of therapeutic miRNAs targeting Huntingtin for development of gene therapy for Huntington's disease. Mol Ther Nucleic Acids. 2016; 5:e297. https://doi.org/10.1038/mtna.2016.7

354. Samaranch L, Blits B, san Sebastian W, Hadaczek P, Bringas J, Sudhakar V, et al. MR-guided parenchymal delivery of adeno-associated viral vector serotype 5 in non-human primate brain. Gene Ther. 2017; 24:253-61. https://doi.org/10.1038/gt.2017.14

355. Taubel J, Hauke W, Rump S, Viereck J, Batkai S, Poetzsch J, et al. Novel antisense therapy targeting microRNA-132 in patients with heart failure: Results of a first-in-human phase 1b randomized, double-blind, placebo-controlled study. Eur Heart J. 2021; 42:178-88. https://doi.org/10.1093/eurheartj/ehaa898

356. Batkari S, Genschel C, Viereck J, Rump S, Bar C, Borchert T, et al. CDR132L improves systolic and diastolic function in a large animal model of chronic heart failure. Eur Heart J. 2021; 42:192-201. https://doi.org/10.1093/eurheartj/ehaa791

357. Mandal AK. Selenium nanoparticles as delivery system against various diseases. Glob J Pharmaceu Sci. 2023; 10(40):555794. https://doi.org/10.19080/GJPPS.2023.10.555791

358. Zheng W, Yin T, Chen Q, Qin X, Huang X, Zhao S, et al. Co-delivery of Se nanoparticles and pooled siRNAs for overcoming drug resistance mediated by P-glycoprotein and class IIIβ-tubulin in drug-resistant breast cancers. Acta Biomater. 2016; 31:197-210. https://doi.org/10.1016/j.actbio.2015.11.041

359. Huang Y, Fu Y, Li M, Jiang D, Kutyreff CJ, Engle JW, et al. Chirality-driven transportation and oxidation prevention by chiral selenium nanoparticles. Angew Chem Int Edit. 2020; 132:1. https://doi.org/10.1002/ange.202081162

360. Yan L, Da H, Zhang S, Lopez VM, Wang W. Bacterial magnetosome and its potential application. Microbiol Res. 2017; 203:19-28. https://doi.org/10.1016/j.micres.2017.06.005

361. Reddy LH, Arias JL, Nocolas J, Couvreur P. Magnetic nanoparticles: Design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications. Chem Rev. 2012; 112:5818-78. https://doi.org/10.1021/cr300068p

362. Lyu C, Lu G, Bao W, Li F, Wang S, Zhang F, et al. Engineering magnetosomes with chimeric membrane and hyaluronidase for efficient delivery of HIF-1 siRNA into deep hypoxic tumors. Chem Eng J. 2020; 398:125453. https://doi.org/10.1016/j.cej.2020.125453

363. Rothemund PWK. Folding DNA to create nanoscale shapes and patterns. Nature. 2006; 440:297-302. https://doi.org/10.1038/nature04586

364. Rahman MA, Wang P, Zhao Z, Wang D, Mannapaneni S, Zhang C, et al. Systemic delivery of Bcl2-targeting siRNA by DNA nanoparticles suppresses cancer cell growth. Angew Chem Int Edit. 2017; 132:12675. https://doi.org/10.1002/ange.202006993

365. Zhang Y, Yu J, Wen D, Chen G, Gu Z. The potential of a microneedle patch for reducing obesity. Expert Opin Drug Deliv. 2018; 15:431-3. https://doi.org/10.1080/17425247.2018.1449831

366. Than A, Liang K, Xu S, Sun L, Duan H, Xi F, et al. Transdermal delivery of anti-obesity compounds to subcutaneous adipose tissue with polymeric microneedle patches. Small Methods. 2017; 1:1700269. https://doi.org/10.1002/smtd.201700269

367. Yang T, Huang D, Li C, Zhao D, Li J, Zhang M, et al. Rolling microneedle electrode array (RoMEA) empowered nucleic acid delivery and cancer immunotherapy. Nano Today. 2021; 36:101017. https://doi.org/10.1016/j.nantod.2020.101017

Published

2025-08-15
Statistics
Abstract Display: 415
PDF Downloads: 370
PDF Downloads: 51

How to Cite

1.
Mandal AK, Chakraborty SK. Biogenesis and implication of miRNAs in the development of diseases and their theranostic inhibitions. J. Drug Delivery Ther. [Internet]. 2025 Aug. 15 [cited 2026 Feb. 1];15(8):267-93. Available from: https://www.jddtonline.info/index.php/jddt/article/view/7336

Issue

Vol. 15 No. 8 (2025): Volume 15, Issue 8, August 2025

Section

Review

Copyright (c) 2025 Ardhendu Kumar Mandal , Sunit Kumar Chakraborty

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Authors who publish with this journal agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).

How to Cite

1.
Mandal AK, Chakraborty SK. Biogenesis and implication of miRNAs in the development of diseases and their theranostic inhibitions. J. Drug Delivery Ther. [Internet]. 2025 Aug. 15 [cited 2026 Feb. 1];15(8):267-93. Available from: https://www.jddtonline.info/index.php/jddt/article/view/7336
Crossref
Scopus
Google Scholar
Europe PMC

Most read articles by the same author(s)