Association of polymorphic loci of genes miR-27a rs895819 and miR-146a rs2910164 with the risk of development of ovarian cancer
https://doi.org/10.18699/SSMJ20250416
Abstract
Ovarian cancer remains one of the most common causes of death from gynecological cancer in women worldwide. Its course depends on many factors, including genetic and epigenetic disorders. MicroRNAs are currently considered one of the most promising prognostic and diagnostic markers for solid tumors. The aim of the study was to analyze the association of polymorphic loci of the microRNA-27a rs895819 and microRNA-146a rs2910164 genes with the risk of developing ovarian cancer.
Material and Methods. Genotyping was performed by determining single nucleotide polymorphisms using the KASP method. For pairwise comparison of the frequency of occurrence of genotypes and alleles in patients with ovarian cancer and in the control group, the χ2 test was used for 2×2 contingency tables. If there are statistically significant differences between the compared samples, the odds ratio (OR) and the boundaries of the 95 % confidence interval (95 % CI) were assessed. Quantitative characteristics were compared using the Mann – Whitney test (in the case of two groups) and the Kruskal – Wallis test (in the case of three groups).
Results. As a result of a comparative analysis of the distribution of frequencies of alleles and genotypes of the polymorphic locus rs2910164 of the miR-146a gene in a sample of patients with ovarian cancer and healthy individuals, it was shown that carriage of the homozygous genotype GG and allele G is a risk factor for women of Tatar ethnicity. No significant differences were detected in the distribution of allele frequencies and genotypes of the rs895819 polymorphic locus of the miR-27a gene.
Conclusions. The polymorphic locus of microRNA-146a rs2910164 is associated with an increased risk of ovarian cancer in women of Tatar ethnicity.
About the Authors
E. T. AminovaRussian Federation
Elvira T. Aminova, candidate of biological sciences
450076, Ufa, Zaki Validi st., 32
Yu. Yu. Fedorova
Russian Federation
Yulia Yu. Fedorova, candidate of biological sciences
450076, Ufa, Zaki Validi st., 32
A. V. Sagitova
Russian Federation
Alina V. Sagitova
450076, Ufa, Zaki Validi st., 32
E. A. Andreeva
Russian Federation
Ekaterina A. Andreeva
450076, Ufa, Zaki Validi st., 32
Ya. V. Valova
Russian Federation
Yana V. Valova, candidate of biological sciences
450076, Ufa, Zaki Validi st., 32,
450106, Ufa, Stepana Kuvykina st., 94
A. Kh. Nurgalieva
Russian Federation
Alfiya Kh. Nurgalieva, candidate of biological sciences
450076, Ufa, Zaki Validi st., 32
R. R. Faiskhanova
Russian Federation
Rania R. Faiskhanova, candidate of medical sciences
450054, Ufa, Oktyabrya ave., 73/1
I. R. Zagitov
Russian Federation
Ilmir R. Zagitov
450054, Ufa, Oktyabrya ave., 73/1
A. R. Romanova
Russian Federation
Albina R. Romanova, candidate of biological sciences
450008, Ufa, Lenina st., 3
D. D. Sakaeva
Russian Federation
Dina D. Sakaeva, doctor of medical sciences, professor
450008, Ufa, Lenina st., 3
E. K. Khusnutdinova
Russian Federation
Elza K. Khusnutdinova, doctor of biological sciences, professor
450076, Ufa, Zaki Validi st., 32,
450054, Ufa, Oktyabrya ave., 71
D. S. Prokofieva
Russian Federation
Darya S. Prokofyeva, candidate of biological sciences
450076, Ufa, Zaki Validi st., 32
References
1. Malignant neoplasms in Russia in 2023 (morbidity and mortality). Eds. A.D. Kaprin, V.V. Starinsky, A.O. Shakhzadova. Moscow: MNIOI im. P.A. Gertsena, 2024. 276 p. [In Russian].
2. National Cancer Institute. Cancer Stat Facts: Ovarian Cancer. Available at: clck.ru/3MB8xD
3. Zhang R., Siu M.K.Y., Ngan H.Y.S., Chan K.K.L. Molecular biomarkers for the early detection of ovarian cancer. Int. J. Mol. Sci. 2022;23(19):12041. doi: 10.3390/ijms231912041
4. Talipov O.A., Ryabchikov D.A., Chulkova S.V., Vorotnikov I.K., Kazakov A.M., Loginov V.I., Kazubskaya T.P., Vinokurov M.S., Osipova A.A., Berdova F.K. Methylation of suppressor microRNA genes in breast cancer. Onkoginekologiya = Oncogynecology. 2020;(2):14–22. [In Russian]. doi: 10.52313/22278710_2020_2_14
5. Liu Y., Gui Y.F., Liao W.Y., Zhang Y.Q., Zhang X.B., Huang Y.P., Wu F.M., Huang Z., Lu Y.F. Association between miR-27a rs895819 polymorphism and breast cancer susceptibility: Evidence based on 6118 cases and 7042 controls. Medicine (Baltimore). 2021;15;100(2):e23834. doi: 10.1097/MD.0000000000023834
6. Feng L., Shen F., Zhou J., Li Y., Jiang R., Chen Y. Hypoxia-induced up-regulation of miR-27a promotes paclitaxel resistance in ovarian cancer. Biosci. Rep. 2020;40(4):BSR20192457. doi: 10.1042/BSR20192457
7. Li R., Wu H., Jiang H., Wang Q., Dou Z., Ma H., Yan S., Yuan C., Yang N., Kong B. FBLN5 is targeted by microRNA-27a-3p and suppresses tumorigenesis and progression in high-grade serous ovarian carcinoma. Oncol. Rep. 2020;44(5):2143–2151. doi: 10.3892/or.2020.7749
8. Qiu L., Wang J., Chen M., Chen F., Tu W. Exosomal microRNA-146a derived from mesenchymal stem cells increases the sensitivity of ovarian cancer cells to docetaxel and taxane via a LAMC2-mediated PI3K/ Akt axis. Int. J. Mol. Med. 2020;46(2):609–620. doi: 10.3892/ijmm.2020.4634
9. Takamizawa S., Kojima J., Umezu T., Kuroda M., Hayashi S., Maruta T., Okamoto A., Nishi H. MiR146a-5p and miR-191-5p as novel diagnostic marker candidates for ovarian clear cell carcinoma. Mol. Clin. Oncol. 2023;20(2):14. doi: 10.3892/mco.2023.2712
10. Chen R., Coleborn E., Bhavsar C., Wang Y., Alim L., Wilkinson A.N., Tran M.A., Irgam G., Atluri S., Wong K., … Wu S.Y. miR-146a inhibits ovarian tumor growth in vivo via targeting immunosuppressive neutrophils and enhancing CD8(+) T cell infiltration. Mol. Ther. Oncolytics. 2023;31:100725. doi: 10.1016/j.omto.2023.09.001
11. Trujillo-Fernández Y.G.V., Yzabal-Barbedillo C., Saucedo-Sarinaña A.M., Tovar-Jácome C.J., Godínez-Rodríguez M.Y., Barros-Núñez P., Gallegos-Arreola M.P., Juárez-Vázquez C.I., Pineda-Razo T.D., Marín-Contreras M.E., Rosales-Reynoso M.A. Functional variants in microRNAs (rs895819, rs11614913 and rs2910164) are associated with susceptibility and clinicopathological features in Mexican patients with colorectal cancer. Arch. Iran. Med. 2023;26(8):439–446. doi: 10.34172/aim.2023.67
12. Ledermann J.A., Raja F.A., Fotopoulo C., Gonzalez-Martin A., Colombo N., Sessa C.; ESMO Guidelines Working Group. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2013;24 Suppl 6:vi24–vi32. doi: 10.1093/annonc/mdt333
13. Mingazheva E.T., Fedorova Yu.Yu., Nurgalieva A.Kh., Valova Ya.V., Andreeva E.A., Sagitova A.V., Faishkhanova R.R., Sakaeva D.D., Khusnutdinova E.K., Prokofieva D.S. The role of microRNAs in the pathogenesis of ovarian cancer. Yakutskiy meditsinskiy zhurnal = Yakut Medical Journal. 2024;(1):80–85. [In Russian]. doi: 10.25789/YMJ.2024.85.21
14. Mertens-Talcott S.U., Chintharlapalli S., Li X., Safe S. The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. Cancer Res. 2007;67(22):11001–11011. doi: 10.1158/0008-5472.CAN-07-2416
15. Wu R., Zhao B., Ren X., Wu S., Liu M., Wang Z., Liu W. MiR-27a-3p targeting GSK3beta promotes triple negative breast cancer proliferation and migration through Wnt/beta-catenin pathway. Cancer Manag. Res. 2020;12:6241–6249. doi: 10.2147/CMAR.S255419
16. Su Q., Xu Z.X., Xiong M.L., Li H.Y., Xu M.Y., Luo S.Z. The oncogenic miR-27a/BTG2 axis promotes obesity-associated hepatocellular carcinoma by mediating mitochondrial dysfunction. Neoplasma. 2022;69(4):820– 831. doi: 10.4149/neo_2022_211227N1837
17. Bi L., Zhou Y., Zhang Y., Zhang X. MiR27a-3p exacerbates cell migration and invasion in right-sided/left-sided colorectal cancer by targeting TGFBR2/TCF7L2. Cell. Mol. Biol. (Noisy-le-grand). 2024;70(1):148–154. doi: 10.14715/cmb/2024.70.1.20
18. Maghsudlu M., Farashahi Yazd. E., Amiriani T. Increased expression of MiR-27a and MiR-24-2 in esophageal squamous cell carcinoma. J. Gastrointest. Cancer. 2020;51(1):227–233. doi: 10.1007/s12029-019-00232-x
19. Cui Y., Pu R., Ye J., Huang H., Liao D., Yang Y., Chen W., Yao Y., He Y. LncRNA FAM230B promotes gastric cancer growth and metastasis by regulating the miR-27a-5p/TOP2A axis. Dig. Dis. Sci. 2021;66(8):2637– 2650. doi: 10.1007/s10620-020-06581-z
20. He W., Qin M., Cai Y., Gao X., Cao S., Wang Z., Chen H., Xu R. Downregulation of HOXC6 by miR27a ameliorates gefitinib resistance in non-small cell lung cancer. Am. J. Cancer Res. 2021;11(9):4329–4346.
21. Setti Boubaker N., Gurtner A., Trabelsi N., Manni I., Ayed H., Saadi A., Naimi Z., Ksontini M., Ayadi M., Blel A., … Ouerhani S. Uncovering the expression patterns and the clinical significance of miR-182, miR-205, miR-27a and miR-369 in patients with urinary bladder cancer. Mol. Biol. Rep. 2020;47(11):8819– 8830. doi: 10.1007/s11033-020-05932-3
22. Zhang L.Y., Chen Y., Jia J., Zhu X., He Y., Wu L.M. MiR-27a promotes EMT in ovarian cancer through active Wnt/-catenin signalling by targeting FOXO1.Cancer Biomark. 2019;24(1):31–42. doi: 10.3233/CBM-181229
23. Sanguansin S., Saelee P., Kritsirivuttinan K., Pongstaporn W. The Association of pre-miR27a gene polymorphism and clinicopathological data in thai breast cancer patients. Asian Pac. J. Cancer Prev. 2023;24(6):2055. doi: 10.31557/APJCP.2023.24.6.2055
24. Chen G., Zhang M., Zhu J., Chen F., Yu D., Zhang A., He J., Hua W., Duan P. Common genetic variants in pre-microRNAs are associated with cervical cancer susceptibility in southern Chinese women. J. Cancer. 2020;11(8):2133. doi: 10.7150/jca.39636
25. Wang B.R., Chang W.S., Liao C.H., Wang Y.C., Gu J., Bau D.T., Tsai C.W. Impacts of Mir146a genotypes on bladder cancer risk in Taiwan. Biomedicines. 2023;11(5):1396. doi: 10.3390/biomedicines11051396
26. Sun X.C., Zhang A.C., Tong L.L., Wang K., Wang X., Sun Z.Q., Zhang H.Y. MiR-146a and mir196a2 polymorphisms in ovarian cancer risk. Genet. Mol. Res. 2016;15(3). doi: 10.4238/gmr.15038468
27. Lukács J., Soltész B., Penyige A., Nagy B., Póka R. Identification of miR-146a and mir-196a-2 single nucleotide polymorphisms at patients with high-grade serous ovarian cancer. J. Biotechnol. 2019;297:54–57. doi: 10.1016/j.jbiotec.2019.03.016
28. Liu H., Sun L., Liu X., Wang R., Luo Q. Associations between non-coding RNAs genetic polymorphisms with ovarian cancer risk: A systematic review and meta-analysis update with trial sequential analysis. Medicine (Baltimore). 2023;102(39):e35257. doi: 10.1097/MD.0000000000035257