Роль микро­РНК, регулирующих гены окислительного стресса при синдроме поликистозных яичников

1. Teede H.J., Tay C.T., Laven J.J.E., Dokras A., Moran L.J., Piltonen T.T. et al. Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Hum. Reprod. 2023; 38(9): 1655-79. https://dx.doi.org/10.1093/humrep/dead156
2. Адамян Л.В., Андреева Е.Н., Абсатарова Ю.С., Григорян О.Р., Дедов И.И., Мельниченко Г.А., Сутурина Л.В., Филиппов О.С., Шереметьева Е.В., Чернуха Г.Е., Ярмолинская М.И. Клинические рекомендации «Синдром поликистозных яичников». Проблемы Эндокринологии. 2022; 68(2): 112-27. https://dx.doi.org/10.14341/probl12874
3. Чернуха Г.Е., Найдукова А.А., Каприна Е.К., Донников А.Е. Молекулярно-генетические предикторы формирования синдрома поликистозных яичников и его андрогенных фенотипов. Акушерство и гинекология. 2021; 4: 120-7. https://dx.doi.org/10.18565/aig.2021.4.120-127
4. Zeber-Lubecka N., Ciebiera M., Hennig E.E. Polycystic ovary syndrome and oxidative stress – from bench to bedside. Int. J. Mol. Sci. 2023; 24(18): 14126. https://dx.doi.org/10.3390/ijms241814126
5. Rudnicka E., Duszewska A.M., Kucharski M., Tyczyński P., Smolarczyk R. Oxidative stress and reproductive function: oxidative stress in polycystic ovary syndrome. Reproduction. 2022; 164(6): F145-54. https://dx.doi.org/10.1530/REP-22-0152
6. Gao Y., Zou Y., Wu G., Zheng L. Oxidative stress and mitochondrial dysfunction of granulosa cells in polycystic ovarian syndrome. Front. Med. (Lausanne). 2023; 10: 1193749. https://dx.doi.org/10.3389/fmed.2023.1193749
7. Bartel D.P. Metazoan microRNAs. Cell. 2018; 173(1): 20-51. https://dx.doi.org/10.1016/j.cell.2018.03.006
8. Gao H., Jiang J., Shi Y., Chen J., Zhao L., Wang C. The LINC00477/miR-128 axis promotes the progression of polycystic ovary syndrome by regulating ovarian granulosa cell proliferation and apoptosis. Reprod. Biol. Endocrinol. 2021; 19(1): 29. https://dx.doi.org/10.1186/s12958-021-00718-z
9. Hess A.L., Larsen L.H., Udesen P.B., Sanz Y., Larsen T.M., Dalgaard L.T. Levels of circulating miR‐122 are associated with weight loss and metabolic syndrome. Obesity. 2020; 28(3): 493-501. https://dx.doi.org/10.1002/oby.22704
10. Гутникова Л.В., Шкурат Т.П. Идентификация транскриптов микроРНК в гранулезных клетках кумулюса при синдроме поликистозных яичников. Живые и биокосные системы. 2025; 51. https://dx.doi.org/10.18522/2308-9709-2025-51-16
11. Cai G., Ma X., Chen B., Huang Y., Liu S., Yang H. et al. MicroRNA-145 negatively regulates cell proliferation through targeting IRS1 in isolated ovarian granulosa cells from patients with polycystic ovary syndrome. Reprod. Sci. 2017; 24(6): 902-10. https://dx.doi.org/10.1177/1933719116673197
12. Fu X., He Y., Wang X., Peng D., Chen X., Li X. et al. MicroRNA-16 promotes ovarian granulosa cell proliferation and suppresses apoptosis through targeting PDCD4 in polycystic ovarian syndrome. Cell. Physiol. Biochem. 2018; 48(2): 670-82. https://dx.doi.org/10.1159/000491894
13. Wang T., Liu Y., Lv M., Xing Q., Zhang Z., He X. et al. miR-323-3p regulates the steroidogenesis and cell apoptosis in polycystic ovary syndrome (PCOS) by targeting IGF-1. Gene. 2019; 683: 87-100. https://dx.doi.org/10.1016/j.gene.2018.10.006
14. Jiang Y.C., Ma J.X. The role of MiR-324-3p in polycystic ovary syndrome (PCOS) via targeting WNT2B. Eur. Rev. Med. Pharmacol. Sci. 2018; 22(11): 3286-93. https://dx.doi.org/10.26355/eurrev_201806_15147
15. Wang M., Zhang S. MiR-145 on the proliferation of ovarian cancer cells by regulating the expression of MMP-2/MMP-9. Cell. Mol. Biol. 2021; 67(6): 141-8. https://dx.doi.org/10.14715/cmb/2021.67.6.19
16. Naji M., Nekoonam S., Aleyasin A., Arefian E., Mahdian R., Azizi E. et al. Expression of miR-15a, miR-145, and miR-182 in granulosa-lutein cells, follicular fluid, and serum of women with polycystic ovary syndrome (PCOS). Arch. Gynecol. Obstet. 2018; 297(1): 221-31. https://dx.doi.org/10.1007/s00404-017-4570-y
17. Chelegahi A.M., Ebrahimi S.O., Reiisi S., Nezamnia M. A glance into the roles of microRNAs (exosomal and non-exosomal) in polycystic ovary syndrome. Obstet. Gynecol. Sci. 2024; 67(1): 30-48. https://dx.doi.org/10.5468/ogs.23193
18. He M., Wu N., Leong M.C., Zhang W., Ye Z., Li R. et al. miR-145 improves metabolic inflammatory disease through multiple pathways. J. Mol. Cell Biol. 2020; 12(2): 152-62. https://dx.doi.org/10.1093/jmcb/mjz015
19. Wang W., Ge L., Zhang L., Liu L., Zhang X., Ma X. MicroRNA-16 represses granulosa cell proliferation in polycystic ovarian syndrome through inhibition of the PI3K/Akt pathway by downregulation of Apelin13. Hum. Fertil. (Camb). 2023; 26(3): 611-21. https://dx.doi.org/10.1080/14647273.2021.1998661
20. Zehra N., Azhar A., Rehman R. MicroRNA-16, Programmed Cell Death Protein-4 (PDCD-4) and polycystic ovarian syndrome. J. Coll. Physicians Surg. Pak. 2020; 30(8): 880-1. https://dx.doi.org/10.29271/jcpsp.2020.08.880
21. Hasegawa T., Kamada Y., Hosoya T., Fujita S., Nishiyama Y., Iwata N. et al. A regulatory role of androgen in ovarian steroidogenesis by rat granulosa cells. J. Steroid Biochem. Mol. Biol. 2017; 172: 160-5. https://dx.doi.org/10.1016/j.jsbmb.2017.07.002
22. Zhao Y., Tao M., Wei M., Du S., Wang H., Wang X. Mesenchymal stem cells derived exosomal miR-323-3p promotes proliferation and inhibits apoptosis of cumulus cells in polycystic ovary syndrome (PCOS). Artif. Cells Nanomed. Biotechnol. 2019; 47(1): 3804-13. https://dx.doi.org/10.1080/21691401.2019.1669619
23. Wu L., Tu Z., Bao Y., Zhai Q., Jin L. Long noncoding RNA NEAT1 decreases polycystic ovary syndrome progression via the modulation of the microRNA‐324‐3p and BRD3 axis. Cell Biol. Int. 2022; 46(12): 2075-84. https://dx.doi.org/10.1002/cbin.11893
24. Chakraborti S., ed. Handbook of oxidative stress in cancer: therapeutic aspects. Singapore: Springer Nature; 2022. 4120 p. https://dx.doi.org/10.1007/978-981-16-5422-0
25. Carbonell T., Gomes A.V. MicroRNAs in the regulation of cellular redox status and its implications in myocardial ischemia-reperfusion injury. Redox Biol. 2020; 36: 101607. https://dx.doi.org/10.1016/j.redox.2020.101607
26. Kushwaha P.P., Verma S., Gupta S. MicroRNA targeting nicotinamide adenine dinucleotide phosphate oxidases in cancer. Antioxid. Redox Signal. 2020; 32(18): 1328-43. https://dx.doi.org/10.1089/ars.2019.7918
27. Youn S.W., Li Y., Kim Y.M., Sudhahar V., Abdelsaid K., Kim H.W. et al. Modification of cardiac progenitor cell-derived exosomes by miR-322 provides protection against myocardial infarction through Nox2-dependent angiogenesis. Antioxidants. 2019; 8(1): 18. https://dx.doi.org/10.3390/antiox8010018
28. Xu X., Zhang G., Chen Y., Xu W., Liu Y., Ji G. et al. Can proline dehydrogenase – a key enzyme involved in proline metabolism – be a novel target for cancer therapy? Front. Oncol. 2023; 13: 1254439. https://dx.doi.org/10.3389/fonc.2023.1254439
29. Kern F., Aparicio-Puerta E., Li Y., Fehlmann T., Kehl T., Wagner V. et al. miRTargetLink 2.0 – interactive miRNA target gene and target pathway networks. Nucleic acids research. 2021; 49(W1): W409-16. https://dx.doi.org/10.1093/nar/gkab297
30. Lee S. Cardiovascular disease and miRNAs: possible oxidative stress-regulating roles of miRNAs. Antioxidants. 2024; 13(6): 656. https://dx.doi.org/10.3390/antiox13060656
31. Saha S. Role of microRNA in oxidative stress. Stresses. 2024; 4(2): 269-81. https://dx.doi.org/10.3390/stresses4020016
32. Minjares M., Wu W., Wang J.M. Oxidative stress and MicroRNAs in endothelial cells under metabolic disorders. Cells. 2023; 12(9): 1341. https://dx.doi.org/10.3390/cells12091341
33. Włodarski A., Strycharz J., Wróblewski A., Kasznicki J., Drzewoski J., Śliwińska A. The role of microRNAs in metabolic syndrome-related oxidative stress. Int. J. Mol. Sci. 2020; 21(18): 6902. https://dx.doi.org/10.3390/ijms21186902
34. Matoušková P., Hanousková B., Skálová L. MicroRNAs as potential regulators of glutathione peroxidases expression and their role in obesity and related pathologies. Int. J. Mol. Sci. 2018; 19(4): 1199. https://dx.doi.org/10.3390/ijms19041199
35. Verma S., Thompson C.L., Fu P., MacLennan G.T., Gupta S. miRNAs regulating GSTP1 as potential diagnostic biomarkers in prostate cancer. Prostate. 2025; 85(13): 1235-44. https://dx.doi.org/10.1002/pros.70011
36. Zargari M., Maadi N., Rezapour M., Bagheri A., Fallahpour S., Nosrati M. et al. The regulatory variant-108C/T in the promoter of paraoxonase 1 (PON1) gene has a more important role in regulating PON1 activity compared to rs3735590
37. in 3ʹ-UTR in patients with coronary artery disease. Adv. Biomed. Res. 2024; 13(1): 38. https://dx.doi.org/10.4103/abr.abr_391_22
38. Joseph S., Barai R.S., Bhujbalrao R., Idicula-Thomas S. PCOSKB: A KnowledgeBase on genes, diseases, ontology terms and biochemical pathways associated with PolyCystic Ovary Syndrome. Nucleic Acids Res. 2015; 44(D1): D1032-5. https://dx.doi.org/10.1093/nar/gkv1146
39. Cirillo F., Catellani C., Lazzeroni P., Sartori C., Nicoli A., Amarri S. et al. MiRNAs regulating insulin sensitivity are dysregulated in polycystic ovary syndrome ovaries and are associated with markers of inflammation and insulin sensitivity. Front. Endocrinol. 2019; 10: 879. https://dx.doi.org/10.3389/fendo.2019.00879
40. Wang Q., Fang C., Zhao Y., Liu Z. Correlation study on serum miR-222-3p and glucose and lipid metabolism in patients with polycystic ovary syndrome. BMC Women's Health. 2022; 22(1): 398. https://dx.doi.org/10.1186/s12905-022-01912-w
41. Dubois-Deruy E., Cuvelliez M., Fiedler J., Charrier H., Mulder P., Hebbar E. et al. MicroRNAs regulating superoxide dismutase 2 are new circulating biomarkers of heart failure. Sci Rep. 2017; 7(1): 14747. https://dx.doi.org/10.1038/s41598-017-15011-6
42. Ломтева С.В. Роль генов, связанных с окислительным стрессом, в синдроме поликистозных яичников: понимание генетической предрасположенности и патогенеза. Экологическая генетика. 2025; 23(3): 303-10. https://dx.doi.org/10.17816/ecogen679724
43. Tabrizi Z.P.F., Miraj S., Tahmasebian S., Ghasemi S. Plasma levels of miR-27a, miR-130b, and miR-301a in polycystic ovary syndrome. Int. J. Mol. Cell. Med. 2020; 9(3): 198-206. https://dx.doi.org/10.22088/IJMCM.BUMS.9.3.198
44. Wang M., Sun J., Xu B., Chrusciel M., Gao J., Bazert M. et al. Functional characterization of MicroRNA-27a-3p expression in human polycystic ovary syndrome. Endocrinology. 2018; 159(1): 297-309. https://dx.doi.org/10.1210/en.2017-00219
45. Lavanya K.K., Palaniappan N., Vinodhini V., Silambanan S. Serum microRNAs as diagnostic markers in polycystic ovary syndrome: a narrative review. JCDR. 2025; 19(1): 01-06. https://dx.doi.org/10.7860/JCDR/2025/74412.20507
46. Curtale G., Rubino M., Locati M. MicroRNAs as molecular switches in macrophage activation. Front. Immunol. 2019; 10: 799. https://dx.doi.org/10.3389/fimmu.2019.00799
47. Zhao Y., Dong D., Reece E.A., Wang A.R., Yang P. Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy. Am. J. Obstet. Gynecol. 2018; 218(1): 136.e1-10. https://dx.doi.org/10.1016/j.ajog.2017.10.040
48. Banerjee S., Cui H., Xie N., Tan Z., Yang S., Icyuz M. et al. Emerging roles of microRNAs in the regulation of Toll-like receptor (TLR)-signaling. Front. Biosci. (Landmark Ed). 2021; 26(4): 771-96. https://dx.doi.org/10.2741/4917
49. Cho S.H., An H.J., Kim K.A., Ko J.J., Kim J.H., Kim Y.R. et al. Single nucleotide polymorphisms at miR-146a/196a2 and their primary ovarian insufficiency-related target gene regulation in granulosa cells. PLoS One. 2017; 12(8): e0183479. https://dx.doi.org/10.1371/journal.pone.0183479
50. Ashrafnezhad Z., Naji M., Aleyasin A., Hedayatpour A., Mahdavinezhad F., Gharaei R. et al. Evaluating the differential expression of miR-146a, miR-222, and miR-9 in matched serum and follicular fluid of polycystic ovary syndrome patients: profiling and predictive value. Int. J. Mol. Cell. Med. 2022; 11(4):320-33. https://dx.doi.org/10.22088/IJMCM.BUMS.11.4.320
51. Ciesielska S., Ślezak-Prochazka I., Bil P., Rzeszowska-Wolny J. Micro RNAs in regulation of cellular redox homeostasis. Int. J. Mol. Sci. 2021; 22(11): 6022. https://dx.doi.org/10.3390/ijms22116022
52. Qin Y., Wang Y., Zhao H., Yang Z., Kang Y. Aberrant miRNA-mRNA regulatory network in polycystic ovary syndrome is associated with markers of insulin sensitivity and inflammation. Ann. Transl. Med. 2021; 9(18): 1405. https://dx.doi.org/10.21037/atm-21-1288
53. Bao C., Chen J., Chen D., Lu Y., Lou W., Ding B. et al. MiR-93 suppresses tumorigenesis and enhances chemosensitivity of breast cancer via dual targeting E2F1 and CCND1. Cell Death Dis. 2020; 11(8): 618. https://dx.doi.org/10.1038/s41419-020-02855-6
54. Tan W., Dai F., Yang D., Deng Z., Gu R., Zhao X. et al. MiR-93-5p promotes granulosa cell apoptosis and ferroptosis by the NF-kB signaling pathway in polycystic ovary syndrome. Front. Immunol. 2022; 13: 967151. https://dx.doi.org/10.3389/fimmu.2022.967151
55. Aldakheel F.M., Abuderman A.A., Alduraywish S.A., Xiao Y., Guo W.W. MicroRNA-21 inhibits ovarian granulosa cell proliferation by targeting SNHG7 in premature ovarian failure with polycystic ovary syndrome. J. Reprod. Immunol. 2021; 146: 103328. https://dx.doi.org/10.1016/j.jri.2021.103328
56. La Sala L., Mrakic-Sposta S., Micheloni S., Prattichizzo F., Ceriello A. Glucose-sensing microRNA-21 disrupts ROS homeostasis and impairs antioxidant responses in cellular glucose variability. Cardiovasc Diabetol. 2018; 17: 105. https://dx.doi.org/10.1186/s12933-018-0748-2
57. Тимофеева А.В., Гусар В.А., Прозоровская К.Н. , Балашов И.С., Ломова Н.А., Ганичкина М.Б., Амирасланов Э.Ю., Волочаева М.В., Низяева Н.В., Боровиков П.И., Франкевич В.Е., Тютюнник В.Л., Кан Н.Е., Бобров М.Ю., Сухих Г.Т. Идентификация ассоциированных с преэклампсией микроРНК методом глубокого секвенирования и количественной полимеразной цепной реакции в реальном времени. Акушерство и гинекология. 2016; 8: 60-70. https://dx.doi.org/10.18565/aig.2016.8.60-70
58. Гусар В.А., Тимофеева А.В., Кан Н.Е., Чаговец В.В., Ганичкина М.Б., Франкевич В.Е. Профиль экспрессии плацентарных микроРНК – регуляторов окислительного стресса при синдроме задержки роста плода. Акушерство и гинекология. 2019; 1: 74-80. https://dx.doi.org/10.18565/aig.2019.1.74-80
59. Бобров М.Ю., Балашов И.С., Филиппова Е.С., Альмова И.К., Тимофеева А.В., Гусар В.А., Боровиков П.И., Хилькевич Е.Г., Чупрынин В.Д., Павлович С.В. Оценка экспрессии микроРНК в очагах ретроцервикального эндометриоза. Акушерство и гинекология. 2018; 6: 55-61. https://dx.doi.org/10.18565/aig.2018.6.55-61
60. Филиппова Е.С., Межлумова Н.А., Гамисония А.М., Эльдаров Ч.М., Кузнецова М.В., Трофимов Д.Ю., Павлович С.В., Козаченко И.Ф., Бобров М.Ю., Адамян Л.В. Профилирование микроРНК и мРНК в тканях эутопического и эктопического эндометрия при эндометриоме. Проблемы репродукции. 2019; 25(2): 27-45. https://dx.doi.org/10.17116/repro20192502127

Поступила 28.11.2025

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