MicroRNA-34a Modulates MDM4 Expression via a Target Site in the Open Reading Frame

摘要: Background MDM4, also called MDMX or HDMX in humans, is an important negative regulator of the p53 tumor suppressor. MDM4 overexpressed about 17% all cancers and more frequently some types, such as colon cancer retinoblastoma. known to be post-translationally regulated by MDM2-mediated ubiquitination decrease its protein levels response genotoxic stress, resulting accumulation activation p53. At transcriptional level, gene regulation has been less clearly understood. We have reported that DNA damage triggers loss mRNA a concurrent increase activity. These experiments attempt determine mechanism for down-regulation mRNA. Methodology/Principal Findings Here we report target hsa-mir-34a (miR-34a). contains lengthy 3′ untranslated region; however, find it miR-34a site within open reading frame (ORF) exon 11 responsible repression. Overexpression miR-34a, but not mutant sufficient extent identical those genes. Likewise, are decreased overexpression. Inhibition endogenous increased expression genes MDM4. A portion containing this 8mer-A1 fused luciferase reporter confer responsiveness, being inhibited additional exogenous mir-34a activated inhibition miR-34a. Conclusions/Significance These data establish observed damage-induced potentially provide novel means manipulate without introducing damage.