Role of methylation of MIR-129-2, MIR-9-1, MIR-9-3, MIR-130b, MIR-107, and MIR-1258 miRNA genes in the pathogenesis and progression of breast cancer

Abstract

Epigenome studies have shown that the proportion of hypermethylated microRNA genes is several times higher than of protein-coding genes,
which makes them promising markers of tumors. The aim of this study was to expand the spectrum of the miRNA genes hypermethylated in breast cancer and to investigate their connection with progression of disease. The methylation-specific PCR performed on a set of 70 breast cancer samples showed a significant increase in methylation frequency in tumor samples compared with histologically unchanged breast tissue for 5 of 6 studied microRNA genes – MIR-1258, -130b, -9-1, -9-3, and -129-2 (p < 0.01). Statistically significant (p < 0.05) associations of hypermethylation of 3 genes with parameters of cancer progression were established: for the MIR-9-3 and MIR-1258 genes - with more severe stages (III-IV) of cancer; MIR-107 and MIR-1258 - with a low level of tumor differentiation; MIR-9-3 - with tumor size; MIR-1258 - with metastases to regional lymph nodes or distant organs. The identified methylation features of the studied genes can find clinical application in development of modern approaches to prediction, prevention, and selection of tactics for the treatment of breast cancer.