Antagonistic activities of miR-148a and DNMT1: Ectopic expression of miR-148a impairs DNMT1 mRNA and dwindle cell proliferation and survival.

Functional analyses of noncoding RNAs have associated many micro RNAs (miRNA, miR) with various physiological processes, including proliferation, differentiation, development, cell metabolism, and apoptosis. Aberrant expression of miRNA and imbalance in their functions may lead to cellular aberration and different disease development, including cancer. In silico analysis of miRNA target prediction suggested that miR-148a possess a binding site in the 3' UTR of DNMT1 mRNA which can cause silencing of DNMT1 gene. Accordingly, we performed in vitro cell culture experiments to confirm the effect miR-148a on DNMT1 gene expression in prostate cancer cell lines. We demonstrated that there is a physical association between DNMT1 mRNA and miR-148a. We found that (i) ectopic expression of miR-148a induces programmed cell death and represses cell proliferation by targeting DNMT1; (ii) miR-148a gene is regulated by DNA methylation and DNMT1 in prostate cancer. We conclude that miR-148a is silenced by DNA methylation and ectopic expression of miR-148a suppresses DNMT1 expression and induced apoptotic genes expression in hormone-refractory prostate cancer cells.