The role of methylation in the regulation of genes of long noncoding RNA (lncRNA) is still poorly understood. We revealed new hypermethylated lncRNA genes in ovarian tumors and their effect on metastasis of ovarian cancer. A multiple and significant (p<0.001) increase in methylation of a group of lncRNA genes (MEG3, SEMA3B-AS1, ZNF667-AS1, and TINCR) was shown by quantitative methylation-specific PCR using the non-parametric Mann—Whitney test. Moreover, methylation of SEMA3B-AS1, ZNF667-AS1, and TINCR genes in ovarian cancer tumors was detected for the first time. Comparative analysis of 19 samples of peritoneal metastases and paired primary tumors showed a significant decrease in the methylation level of the same 4 genes: MEG3 (p=0.004), SEMA3B-AS1 (p=0.002), TINCR (p=0.002), and ZNF667-AS1 (p<0.001). Reduced methylation of suppressor lncRNA genes in peritoneal metastases is probably associated with the involvement of these lncRNA in the regulation of plastic reversion of the epithelial-mesenchymal transition to the mesenchymal-epithelial transition. Thus, the effect of lncRNA and their methylation on the development of tumors and metastases of ovarian cancer was demonstrated, which is important for understanding of the pathogenesis and mechanisms of metastasis of ovarian cancer. New properties of lncRNA can find application in the development of new approaches in the therapy of ovarian cancer.
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Braga EA, Fridman MV, Moscovtsev AA, Filippova EA, Dmitriev AA, Kushlinskii NE. LncRNA in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms. Int. J. Mol. Sci. 2020;21(22):8855. doi: https://doi.org/10.3390/ijms21228855
Chen X, Wu W, Cao X, Zhao X, Li W, Deng C, Huang Z. lncRNA mortal obligate RNA transcript was downregulated in ovarian carcinoma and inhibits cancer cell proliferation by downregulating miRNA-21. J. Cell. Biochem. 2019. doi: https://doi.org/10.1002/jcb.28478
Davidson B, Tropé CG, Reich R. Epithelial-mesenchymal transition in ovarian carcinoma. Front. Oncol. 2012;2:33. doi: https://doi.org/10.3389/fonc.2012.00033
Guo W, Liang X, Liu L, Guo Y, Shen S, Liang J, Dong Z. MiR- 6872 host gene SEMA3B and its antisense lncRNA SEMA3BAS1 function synergistically to suppress gastric cardia adenocarcinoma progression. Gastric Cancer. 2019;22(4):705-722. doi: https://doi.org/10.1007/s10120-019-00924-0
Hattermann K, Mehdorn H. M, Mentlein R, Schultka S, Held-Feindt J. A methylation-specific and SYBR-green-based quantitative polymerase chain reaction technique for O6-methylguanine DNA methyltransferase promoter methylation analysis. Anal. Biochem. 2008;377(1):62-71. doi: https://doi.org/10.1016/j.ab.2008.03.014
Li R, Wang Y, Xu Y, He X, Li Y. Silencing the long noncoding RNA, TINCR, a molecular sponge of miR-335, inhibits the malignant phenotype of epithelial ovarian cancer via FGF2 suppression. Int. J. Oncol. 2019;55(5):1110-1124. doi: https://doi.org/10.3892/ijo.2019.4875
Liu X, Ma J, Xu F, Li L. TINCR suppresses proliferation and invasion through regulating miR-544a/FBXW7 axis in lung cancer. Biomed. Pharmacother. 2018;99:9-17. doi: https://doi.org/10.1016/j.biopha.2018.01.049
Loginov VI, Pronina IV, Burdennyy AM, Filippova EA, Kazubskaya TP, Kushlinsky DN, Utkin DO, Khodyrev DS, Kushlinskii NE, Dmitriev AA, Braga EA. Novel miRNA genes deregulated by aberrant methylation in ovarian carcinoma are involved in metastasis. Gene. 2018;662:28-36. doi: https://doi.org/10.1016/j.gene.2018.04.005
Ma N, Li S, Zhang Q, Wang H, Qin H, Wang S. Long noncoding RNA GAS5 inhibits ovarian cancer cell proliferation via the control of microRNA-21 and SPRY2 expression. Exp. Ther. Med. 2018;16(1):73-82. doi: https://doi.org/10.3892/etm.2018.6188
Panagopoulou M, Karaglani M, Balgkouranidou I, Biziota E, Koukaki T, Karamitrousis E, Nena E, Tsamardinos I, Kolios G, Lianidou E, Kakolyris S, Chatzaki E. Circulating cell-free DNA in breast cancer: size profiling, levels, and methylation patterns lead to prognostic and predictive classifiers. Oncogene. 2019;38(18):3387-3401. doi: https://doi.org/10.1038/s41388-018-0660-y
Quinn JJ, Chang HY. Unique features of long non-coding RNA biogenesis and function. Nat. Rev. Genet. 2016;17(1):47-62.doi: https://doi.org/10.1038/nrg.2015.10
Tao P, Yang B, Zhang H, Sun L, Wang Y, Zheng W. The overexpression of lncRNA MEG3 inhibits cell viability and invasion and promotes apoptosis in ovarian cancer by sponging miR-205-5p. Int. J. Clin. Exp. Pathol. 2020;13(5):869-879.
Vogell A, Evans ML. Cancer Screening in Women. Obstet. Gynecol. Clin. North Am. 2019;46(3):485-499. doi: https://doi.org/10.1016/j.ogc.2019.04.007
WHO Classification of Tumours of Female Reproductive Organs. Kurman RJ, Carcangiu ML, Herrington CS, Young RH, eds. WHO Classification of Tumours. WHO, 2014. Vol. 6.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 171, No. 3, pp. 353-358, March, 2021
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Burdennyy, A.M., Filippova, E.A., Ivanova, N.A. et al. Hypermethylation of Genes in New Long Noncoding RNA in Ovarian Tumors and Metastases: A Dual Effect. Bull Exp Biol Med 171, 370–374 (2021). https://doi.org/10.1007/s10517-021-05230-3
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DOI: https://doi.org/10.1007/s10517-021-05230-3