Regulation of miR-186-YY1 axis by the p53 translational isoform increment 40p53: implications in cell proliferation

摘要

We have earlier shown that p53-FL and its translational isoform increment 40p53 are differentially regulated. In this study, we have investigated the cellular effect of increment 40p53 regulation on downstream gene expression, specifically miRNAs. Interestingly, increment 40p53 showed antagonistic regulation of miR-186-5p as compared to either p53 alone or a combination of both the isoforms. We have elucidated the miR-186-5p mediated effect of increment 40p53 in cell proliferation. Upon expression of increment 40p53, we observed a significant decrease in YY1 levels, an established target of miR-186-5p, which is involved in cell proliferation. Further assays with anti-miR-186 established the interdependence of increment 40p53- miR-186-5p-YY1- cell proliferation. The results unravel a new dimension toward the understanding of increment 40p53 functions, which seems to regulate cellular fate independent of p53FL.