[Coordinated Expression and Methylation of microRNAs: Role in Common Biological Processes and Signaling Pathways in...

Breast cancer remains one of the leading causes of cancer mortality among women, and the study of epigenetic mechanisms is an important task of molecular oncology in breast cancer. In this study, we analyzed the expression levels of eight microRNAs (miR-125b-5p, -127-5p, -129-5p, -132-3p, -148a-3p, -193a- 5p, -24-2-5p, and -34b-3p) and methylation of promoter regions of seven microRNA genes in a representative set of 40 and 70 paired samples of tumor and normal breast tissue, respectively, and showed hypermethylation of promoter regions of seven genes and a statistically significant decrease in the expression levels of eight microRNAs in tumors. For three genes (MIR125B-1, MIR129-2, MIR148A), inverse relationships between methylation and expression (rs < -0.5) were revealed, indicating their possible epigenetic regulation. Statistically significant positive correlations of expression levels were revealed for seven pairwise combinations of miRNAs, suggesting their coordinated functioning. Indeed, for the pairs miR-127-5p/miR-125b-5p, miR-148a-3p/miR-125b-5p, miR-148a-3p/miR-132-3p, and miR-34b-3p/miR-193a-5p, common mRNA targets and involvement in biological processes, including pathways associated with epigenetic regulation, proliferation, and metastasis, were revealed. The miRNA-mRNA regulatory network constructed involving DNMTs and EZH2 highlights their potential role in breast cancer progression and demonstrates diagnostic and prognostic significance.