MiR-128 exerts pro-apoptotic effect in a p53 transcription-dependent and -independent manner via PUMA-Bak axis.

ABSTRACT: p53 has attracted tremendous attention due to its master role in tumor development. Activation of p53 in tumor cells has been the prime focus for cancer drug discovery. Recent studies have shown that few miRNAs can regulate p53 activity directly or indirectly. We herein demonstrate that miR-128 positively regulates p53 activity. Our data suggest that miR-128 inhibits SIRT1 expression directly through a miR-128-binding site within the 3' UTR of SIRT1. miR-128 inhibition of SIRT1 led to an increase in acetylated p53 and its transcriptional targets. miR-128 decreased phospho-Akt and phospho-FOXO3A, increased acetylated FOXO3A and promoted FOXO3A translocation to the nucleus. We further demonstrated that miR-128 augments the antitumor effect of compounds that target the p53 pathway. Furthermor

SUBMITTER: Adlakha YK 

PROVIDER: S-EPMC3613825 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature