NF-?B-dependent microRNA-125b up-regulation promotes cell survival by targeting p38? upon ultraviolet radiation.

ABSTRACT: UV-induced stress response involves expression change of a myriad of genes, which play critical roles in modulating cell cycle arrest, DNA repair, and cell survival. Alteration of microRNAs has been found in cells exposed to UV, yet their function in UV stress response remains elusive. Here, we show that UV radiation induces up-regulation of miR-125b, which negatively regulates p38? expression through targeting its 3'-UTR. Increase of miR-125b depends on UV-induced NF-?B activation, which enhances miR-125b gene transcription upon UV radiation. The DNA damage-responsive kinase ATM (ataxia telangiectasia mutated) is indispensable for UV-induced NF-?B activation, which may regulate p38? activation and IKK?-dependent I?B? degradation in response to UV. Consequently, repression of p38? by miR-125b prohibits prolonged hyperactivation of p38? by UV radiation, which is required for protecting cells from UV-induced apoptosis. Altogether, our data support a critical role of NF-?B-dependent up-regulation of miR-125b, which forms a negative feedback loop to repress p38? activation and promote cell survival upon UV radiation.

SUBMITTER: Tan G 

PROVIDER: S-EPMC3463348 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature