Tumor suppressor p53 induces miR-1915 processing to inhibit Bcl-2 in the apoptotic response to DNA damage.

The antiapoptotic protein Bcl-2 is overexpressed in human cancers, and confers resistance to antitumor agents in cancer cells. Bcl-2 is negatively regulated by the tumor suppressor p53 in response to DNA damage during apoptotic cell death. However, this molecular mechanism remains unclear. The available evidence indicates that miR-1915 represses Bcl-2 expression at the post-transcriptional level in human colorectal carcinoma cells, which is correlated with drug resistance. Here, we show that p53 controls miR-1915 expression in response to DNA damage. Induction of p53 affects the expression of precursor and mature, but not primary, miR-1915. Inhibition of miR-1915 abrogates downregulation of Bcl-2 expression following treatment with genotoxin. These findings demonstrate that p53 negatively regulates Bcl-2 expression by targeting miR-1915 processing from primary into precursor miRNA. Taken together, the findings of the current study reveal a novel mechanism whereby p53 negatively modulates Bcl-2 by controlling miR-1915.