The role of MicroRNAs in the regulation of oxidative stress in endometriosis
https://doi.org/10.34680/2076-8052.2025.2(140).273-290
Abstract
Micro ribonucleic acids (microRNA) are short, single-stranded non-coding RNA molecules that play a critical role in regulating a wide range of biological processes essential for maintaining homeostasis under physiological conditions. In addition to their functions in normal cellular regulation, miRNAs are increasingly recognized for their involvement in the pathogenesis of various diseases, particularly through their influence on oxidative stress mechanisms. Oxidative stress results from an imbalance between the excessive production of reactive oxygen species and a deficiency in antioxidant defenses. It is now acknowledged as a key contributor to the development and progression of endometriosis. Recent studies have identified several microRNAs (miR-21, miR-23a, miR-30a, miR-34a, miR-125b, miR-132, miR-146a, miR-155, miR-200c, miR-205, miR-484, and miR-6516-5p) that regulate oxidative stress by directly or indirectly modulating the transcription of antioxidant enzymes. Given their role in modulating redox status in endometriosis, these microRNAs may serve as valuable diagnostic and prognostic markers for the condition, aiding in the assessment of severity and stage progression.
About the Authors
M. V. Osikov
South-Ural state medical university; Chelyabinsk regional clinical hospital
Russian Federation
Russian Federation
Chelyabinsk
I. V. Kurnosenko
South-Ural state medical university; Regional perinatal center
Russian Federation
Russian Federation
Chelyabinsk
V. A. Kryukov
South-Ural state medical university; Chelyabinsk regional clinical hospital
Russian Federation
Russian Federation
Chelyabinsk
References
1. Ajdary M., Kashi A. M., Derakhshan R., Chaichian S., Tahermanesh K., Mehdizadeh M., Minaeian S., Govahi A. NLRP3 concentration, oxidants, and antioxidants in plasma of endometriosis patients undergoing treatment with dienogest // Journal of gynecology obstetrics and human reproduction. 2024. 53 (3). 102744. DOI: 10.1016/j.jogoh.2024.102744
2. Endometreosis: clinical guidelines of Ministry of Health of the Russian Federation // Russian Society of obstetrician-gynecologists. 2024. URL: https://roag-portal.ru/recommendations_gynecology (Accessed: 21.12.2024). (In Russian).
3. Senyel D., Boyd J. H., Graham M. Informational support for women with endometriosis: a scoping review // BMC women’s health. 2025. 25 (1). 48. DOI: 10.1186/s12905-025-03581-x
4. Chen P., Wei X., Li X.-K., Zhou Y.-H., Liu Q.-F., Ou-Yang L. Identification of potential druggable targets for endometriosis through Mendelian randomization analysis // Frontiers in endocrinology. 2025. 15. 1371498. DOI: 10.3389/fendo.2024.1371498
5. Cuffaro F., Russo E., Amedei A. Endometriosis, pain, and related psychological disorders: unveiling the interplay among the microbiome, inflammation, and oxidative stress as a common thread // International journal of molecular sciences. 2024. 25 (12). 6473. DOI: 10.3390/ijms25126473
6. Clower L., Fleshman T., Geldenhuys W. J., Santanam N. Targeting oxidative stress involved in endometriosis and its pain // Biomolecules. 2022. 12 (8). 1055. DOI: 10.3390/biom12081055
7. Wyatt J., Fernando S. M., Powell S. G., Hill C. J., Arshad I., Probert C., Ahmed S., Hapangama D. K. The role of iron in the pathogenesis of endometriosis: a systematic review // Human reproduction open. 2023. 2023 (3). hoad033. DOI: 10.1093/hropen/hoad033
8. Biasioli A., Xholli A., Previtera F., Balzano A., Capodicasa V., Tassi A., Londero A. P., Cagnacci A. Systemic oxidative stress in women with ovarian and pelvic endometriosis: role of hormonal therapy // Journal of clinical medicine. 2022. 11 (24). 7460. DOI: 10.3390/jcm11247460
9. Ansariniya H., Yavari A., Javaheri A., Zare F. Oxidative stress‐related effects on various aspects of endometriosis // American journal of reproductive immunology. 2022. 88 (3). e13593. DOI: 10.1111/aji.13593
10. Assaf L., Eid A. A., Nassif J. Role of AMPK/mTOR, mitochondria, and ROS in the pathogenesis of endometriosis // Life science journal. 2022. 306 (5). 120805. DOI: 10.1016/j.lfs.2022.120805
11. Chen C., Zhou Y., Hu C., Wang Y., Yan Z., Li Z., Wu R. Mitochondria and oxidative stress in ovarian endometriosis // Free radical biology and medicine. 2019. 136. 22–34. DOI: 10.1016/j.freeradbiomed.2019.03.027
12. Jiang X., Stockwell B. R., Conrad M. Ferroptosis: mechanisms, biology and role in disease // Nature reviews molecular cell biology. 2021. 22 (4). 266–282. DOI: 10.1038/s41580-020-00324-8
13. Ni C., Li D. Ferroptosis and oxidative stress in endometriosis: A systematic review of the literature // Medicine (Baltimore). 2024. 103 (11). e37421. DOI: 10.1097/MD.0000000000037421
14. Dutta S., Sengupta P., Mottola F., Das S., Hussain A., Ashour A., Rocco L., Govindasamy K., Rosas I. M., Roychoudhury S. Crosstalk between oxidative stress and epigenetics: unveiling new biomarkers in human infertility // Cells. 2024. 13 (22). 1846. DOI: 10.3390/cells13221846
15. Cui C., Zhong B., Fan R., Cui Q. HMDD v4.0: a database for experimentally supported human microRNA-disease associations // Nucleic acids research. 2024. 52 (D1). D1327–D1332. DOI: 10.1093/nar/gkad717
16. Begum M. I. A., Chuan L., Hong S.-T., Chae H.-S. The pathological role of miRNAs in endometriosis // Biomedicines. 2023. 11 (11). 3087. DOI: 10.3390/biomedicines11113087
17. Cui S., Yu S., Huang H.-Y., Lin Y.-C.-D., Huang Y., Zhang B., Xiao J., Zuo H., Wang J., Li Z., Li G., Ma J., Chen B., Zhang H., Fu J., Wang L., Huang H.-D. MiRTarBase 2025: updates to the collection of experimentally validated microRNA–target interactions // Nucleic acids research. 2025. 53 (D1). D147–D156. DOI: 10.1093/nar/gkae1072
18. Luo Y., Wang D., Chen S., Yang Q. The role of miR-34c-5p/Notch in epithelial-mesenchymal transition (EMT) in endometriosis // Celluar signalling. 2020. 72. 109666. DOI: 10.1016/j.cellsig.2020.109666
19. Correia De Sousa M., Gjorgjieva M., Dolicka D., Sobolewski C., Foti M. Deciphering miRNAs’ action through miRNA editing // International journal of molecular sciences. 2019. 20 (24). 6249. DOI: 10.3390/ijms20246249
20. Zhu Q., Kirby J. A., Chu C., Gou L.–T. Small Noncoding RNAs in reproduction and infertility // Biomedicines. 2021. 9 (12). 1884. DOI: 10.3390/biomedicines9121884
21. Marí-Alexandre J., Carcelén A. P., Agababyan C., Moreno-Manuel A., García-Oms J., Calabuig-Fariñas S., Gilabert-Estellés J. Interplay between microRNAs and oxidative stress in ovarian conditions with a focus on ovarian cancer and endometriosis // International journal of molecular sciences. 2019. 20 (21). 5322. DOI: 10.3390/ijms20215322
22. Wang X., Yang J., Li H., Mu H., Zeng L., Cai S., Su P., Li H., Zhang L., Xiang W. miR-484 mediates oxidative stress-induced ovarian dysfunction and promotes granulosa cell apoptosis via SESN2 downregulation // Redox biology. 2023. 62. 102684. DOI: 10.1016/j.redox.2023.102684
23. Saare M., Rekker K., Laisk-Podar T., Rahmioglu N., Zondervan K., Salumets A., Götte M., Peters M. Challenges in endometriosis miRNA studies – From tissue heterogeneity to disease specific miRNAs // Biochimica et biophysica acta – molecular basis of disease. 2017. 1863 (9). 2282–2292. DOI: 10.1016/j.bbadis.2017.06.018
24. O’Brien J., Hayder H., Zayed Y., Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation // Frontiers in endocrinology. 2018. 9. 402. DOI: 10.3389/fendo.2018.00402
25. Pong S. K., Gullerova M. Noncanonical functions of microRNA pathway enzymes – Drosha, DGCR 8, Dicer and Ago proteins // FEBS letters. 2018. 592 (17). 2973–2986. DOI: 10.1002/1873-3468.13196
26. Clarke A. W., Høye E., Hembrom A. A., Paynter V. M., Vinther J., Wyrożemski Ł., Biryukova I. Formaggioni A., Ovchinnikov V., Herlyn H., Pierce A., Wu C., Aslanzadeh M., Cheneby J., Martinez P., Friedlander M. R., Hovig E., Hackenberg M., Umu S.U., Johansen, M., Peterson K. J., Fromm B. MirGeneDB 3.0: improved taxonomic sampling, uniform nomenclature of novel conserved microRNA families and updated covariance models // Nucleic acids research. 2025. 53 (D1). D116–D128. DOI: 10.1093/nar/gkae1094
27. Kozomara A., Birgaoanu M., Griffiths-Jones S. miRBase: from microRNA sequences to function // Nucleic acids research. 2019. 47 (D1). D155–D162. DOI: 10.1093/nar/gky1141
28. Didziokaite G., Biliute G., Gudaite J., Kvedariene V. Oxidative stress as a potential underlying cause of minimal and mild endometriosis-related infertility // International journal of molecular sciences. 2023. 24 (4). 3809. DOI: 10.3390/ijms24043809
29. Carlomosti F., D’Agostino M., Beji S., Torcinaro A., Rizzi R., Zaccagnini G., Maimone B., Di Stefano V., De Santa F., Cordisco S., Antonini A., Ciarapica R., Dellambra E., Martelli F., Avitabile D., Capogross, M. C., Magenta A. Oxidative stress-induced miR-200c disrupts the regulatory loop among SIRT1, FOXO1, and eNOS // Antioxidants and redox signaling. 2017. 27 (6). 328–344. DOI: 10.1089/ars.2016.6643
30. Lan J., Huang Z., Han J., Shao J., Huang C. Redox regulation of microRNAs in cancer // Cancer letters. 2018. 418. 250–259. DOI: 10.1016/j.canlet.2018.01.010
31. Babaee M., Chamani E., Ahmadi R., Bahreini E., Balouchnejadmojarad T., Nahrkhalaji A. S., Fallah S. The expression levels of miRNAs-27a and 23a in the peripheral blood mononuclear cells (PBMCs) and their correlation with FOXO1 and some inflammatory and anti-inflammatory cytokines in the patients with coronary artery disease (CAD) // Life science. 2020. 256. 117898. DOI: 10.1016/j.lfs.2020.117898
32. Luo H., Han Y., Liu J., Zhang Y. Identification of microRNAs in granulosa cells from patients with different levels of ovarian reserve function and the potential regulatory function of miR-23a in granulosa cell apoptosis // Genetics. 2019. 686. 250–260. DOI: 10.1016/j.gene.2018.11.025
33. Long B., Gan T.-Y., Zhang R.-C., Zhang Y.-H. MiR-23a regulates cardiomyocyte poptosis by targeting manganese superoxide dismutase // Molecular cells. 2017. 40 (8). 542–549. DOI: 10.14348/molcells.2017.0012
34. Vezza T., De Marañón A. M., Canet F., Díaz-Pozo P., Marti M., D’Ocon P., Apostolova N., Rocha M., Víctor V. M. MicroRNAs and oxidative stress: an intriguing crosstalk to be exploited in the management of type 2 diabetes // Antioxidants. 2021. 10 (5). 802. DOI: 10.3390/antiox10050802
35. Battaglia R., Caponnetto A., Caringella A.M., Cortone A., Ferrara C., Smirni S., Iannitti R., Purrello M., D’Amato G., Fioretti B., Di Pietro C. Resveratrol treatment induces mito-miRNome modification in follicular fluid from aged women with a poor prognosis for in vitro fertilization cycles // Antioxidants. 2022. 11 (5). 1019. DOI: 10.3390/antiox11051019
36. Tatone C., Di Emidio G. Mitochondria biology in reproductive function // Antioxidants. 2022. 11 (10). 1978. DOI: 10.3390/antiox11101978
37. Wan Y., Gu C., Kong J., Sui J., Zuo L., Song Y., Chen J. Long noncoding RNA ADAMTS9-AS1 represses ferroptosis of endometrial stromal cells by regulating the miR-6516-5p/GPX4 axis in endometriosis // Scientific reports. Nature publishing group. 2022. 12 (1). 2618. DOI: 10.1038/s41598-022-04963-z
38. Zubrzycka A., Migdalska-Sęk M., Jędrzejczyk S., Brzeziańska-Lasota E. The expression of TGF-β1, SMAD3, ILK and miRNA-21 in the ectopic and eutopic endometrium of women with endometriosis // International journal of molecular sciences. 2023. 24 (3). 2453. DOI: 10.3390/ijms24032453
39. Vanhie A., O D., Peterse D., Beckers A., Cuéllar A., Fassbender A., Meuleman C., Mestdagh P., D’Hooghe T. Plasma miRNAs as biomarkers for endometriosis // Human reproduction. 2019. 34 (9). 1650–1660. DOI: 10.1093/humrep/dez116
40. Shen L., Yang S., Huang W., Xu W., Wang Q., Song Y., Liu Y. MicroRNA23a and microRNA23b deregulation derepresses SF-1 and upregulates estrogen signaling in ovarian endometriosis // The journal of clinical endocrinology and metabolism. 2013. 98 (4). 1575–1582. DOI: 10.1210/jc.2012-3010
41. Huang Y., Zhang D., Zhou Y., Peng C. Identification of a serum exosome-derived incRNA‒miRNA‒mRNA ceRNA network in patients with endometriosis // Clinical and experimental obstetrics & gynecology. 2024. 51 (2). 51. DOI: 10.31083/j.ceog5102051
42. Zhuo Z., Wang C., Yu H. Plasma microRNAs can be a potential diagnostic biomarker for endometriosis // Ginekologia (Polska). 2022. 93 (6). 450–459. DOI: 10.5603/GP.a2021.0127
43. Antonio L. G. L., Meola J., Rosa-e-Silva A. C. J. D. S., Nogueira A. A., Candido Dos Reis F. J., Poli-Neto O. B., Rosa-e-Silva J. C. Altered differential expression of genes and microRNAs related to adhesion and apoptosis pathways in patients with different phenotypes of endometriosis // International journal of molecular sciences. 2023. 24 (5). 4434. DOI: 10.3390/ijms24054434
44. Misir S., Hepokur C., Oksasoglu B., Yildiz C., Yanik A., Aliyazicioglu Y. Circulating serum miR-200c and miR-34a-5p as diagnostic biomarkers for endometriosis // Journal of gynecology obstetrics and human reproduction. 2021. 50 (4). 102092. DOI: 10.1016/j.jogoh.2021.102092
45. Rezk N. A., Lashin M. B., Sabbah N. A. MiRNA 34-a regulate SIRT-1 and Foxo-1 expression in endometriosis // Non-coding RNA research. 2021. 6 (1). 35–41. DOI: 10.1016/j.ncrna.2021.02.002
46. Cipollini M., Luisi S., Piomboni P., Luddi A., Landi D., Melaiu O., Figlioli G., Garritano S., Cappelli V., Viganò P., Gemignani F., Petraglia F., Landi S. Functional polymorphism within NUP210 encoding for nucleoporin GP210 is associated with the risk of endometriosis // International journal of fertility and sterility. 2019. 112 (2). 343-352.e1. DOI: 10.1016/j.fertnstert.2019.04.011
47. Hajimaqsoudi E., Darbeheshti F., Kalantar S. M., Javaheri A., Mirabutalebi S. H., Sheikhha M. H. Investigating the expressions of miRNA-125b and TP53 in endometriosis. Does it underlie cancer-like features of endometriosis? A case–control study // International journal of reproductive biomedicine. 2020. 18 (10). 825–836. DOI: 10.18502/ijrm.v13i10.7767
48. Kluz N., Kowalczyk E., Wasilewska M., Gil–Kulik P. Diagnostic value and molecular function of microRNAs in endometrial diseases: a systematic review // Cancers. 2024. 16 (13). 2416. DOI: 10.3390/cancers16132416
49. Hon J.–X., Wahab N. A., Karim A. K. A., Mokhtar N. M., Mokhtar M. H. MicroRNAs in endometriosis: insights into inflammation and progesterone resistance // International journal of molecular sciences. 2023. 24 (19). 15001. DOI: 10.3390/ijms241915001
50. Wang H., Sha L., Huang L., Yang S., Zhou Q., Luo X., Shi B. LINC00261 functions as a competing endogenous RNA to regulate BCL2L11 expression by sponging miR-132-3p in endometriosis // American journal of translational research. 2019. 11 (4). 2269–2279.
51. Wang Y., Ma C.H., Qiao J. [Differential expression of microRNA in eutopic endometrium tissue during implantation window for patients with endometriosis related infertility] // Zhonghua Fu Chan Ke Za Zhi. 2016. 51 (6). 436–441. DOI: 10.3760/cma.j.issn.0529-567X.2016.06.007 (In Chinese).
52. Ji J., Wang H., Yuan M., Li J., Song X., Lin K. Exosomes from ectopic endometrial stromal cells promote M2 macrophage polarization by delivering miR-146a-5p // International immunopharmacology. 2024. 128. 111573. DOI: 10.1016/j.intimp.2024.111573
53. Brunty S., Ray Wright K., Mitchell B., Santanam N. Peritoneal modulators of EZH2-miR-155 cross-talk in endometriosis // International journal of molecular sciences. 2021. 22 (7). 3492. DOI: 10.3390/ijms22073492
54. Nisenblat V., Sharke, D. J., Wang Z., Evans S. F., Healey M., Ohlsson Teague E. M. C., Print C. G., Robertson S. A., Hull M. L. Plasma miRNAs display limited potential as diagnostic tools for endometriosis // Journal of clinical endocrinology and metabolism. 2019. 104 (6). 1999–2022. DOI: 10.1210/jc.2018-01464
55. Hawkins S. M., Creighton C. J., Han D. Y., Zariff A., Anderson M. L., Gunaratne P. H., Matzuk M. M. Functional microRNA involved in endometriosis // Journal of molecular endocrinology. 2011. 25 (5). 821–832. DOI: 10.1210/me.2010-0371
56. Zhou C.-F., Liu M.-J., Wang W., Wu S., Huang Y.-X., Chen G.-B., Liu L.-M., Peng D.-X., Wang X.-F., Cai X.-Z., Li X.-X., Feng W.-Q., Ma Y. MiR-205-5p inhibits human endometriosis progression by targeting ANGPT2 in endometrial stromal cells // Stem cell research and therapy. 2019. 10 (1). 287. DOI: 10.1186/s13287-019-1388-5
57. Cui P., Song Y., Wang X. Predictive value of serum and tissue miR-205 for postoperative recurrence of ovarian-type endometriosis // Journal of Kunming medical university. 2024. 45 (10). 105–110. DOI: 10.12259/j.issn.2095-610X.S20241016
58. Abo C., Biquard L., Girardet L., Chouzenoux S., Just P.-A., Chapron C., Vaiman D., Borghese B. Unbiased in silico analysis of gene expression pinpoints circulating miRNAs targeting KIAA1324, a new gene drastically downregulated in ovarian endometriosis // Biomedicines. 2022. 10 (9). 2065. DOI: 10.3390/biomedicines10092065
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For citations:
Osikov M.V., Kurnosenko I.V., Kryukov V.A. The role of MicroRNAs in the regulation of oxidative stress in endometriosis. Title in english. 2025;(2(140)):273-290. (In Russ.) https://doi.org/10.34680/2076-8052.2025.2(140).273-290
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