Hypermethylation of miR-107, miR-130b, miR-203a, miR-1258 Genes Associated with Ovarian Cancer Development and Metastasis

Abstract

It is known that microRNAs (miRNAs) are able to dynamically regulate gene expression. At the same time, methylation can reduce expression of miRNA encoding genes and, therefore, reduce their inhibitory effects on mRNAs of target genes, including those of oncogenes, that promoting the development of tumors of different localization. The role of miRNA hypermethylation in the pathogenesis of ovarian cancer is not completely understood; so we conducted a search for new hypermethylated and potentially suppressor miRNA genes in ovarian tumors. Four new miRNA genes (MIR-107, MIR-130b, MIR-203a, MIR-1258) commonly hypermethylated (28‒52% ) in tumor tissues vs 4‒7% in paired histologically normal tissues, p < 0.01, were identified in a representative set of 54 ovarian cancer samples using methylation-specific PCR. It was shown that hypermethylation of MIR-130b, MIR-203a, and MIR-1258 genes is significantly (p ≤ 0.05) associated with metastasis of ovarian cancer. These results suggest the involvement of four miRNAs (miR-107, miR-130b, miR-203a, and miR-1258) and hypermethylation of their encoding genes in the pathogenesis of ovarian cancer.