期刊
CELLULAR SIGNALLING
卷 25, 期 6, 页码 1476-1485出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2013.03.015
关键词
HuR; miR-130a; HOXA5; Retinoic acid
类别
资金
- Ministry of Science and Technology of China [2011CB966302, 2010CB912804]
- National Natural Science Foundation of China [31030046, 81101525]
Retinoic acid (RA) has been used as a chemopreventive agent for breast cancer. It has been shown that HOXA5 is a critical mediator of RA-induced cell growth inhibition. However, the molecular mechanisms underlying RA-induced HOXA5 expression remain largely unknown. Here we report that in addition to transcriptional regulation, post-transcriptional regulation also contributes to RA-induced HOXA5 expression. miR-130a, ac-Myc responsive miRNA, represses HOXA5 cellular levels under unstressed condition. Upon RA treatment, c-Myc is quickly degraded via the proteasome-dependent pathway. This in turn decreases miR-130a levels and de-represses the translation of HOXA5. We also show that the de-repression of HOXA5 translation is dependent on the-RNA-binding protein Human antigen R (HuR), which binds to 3'UTR of HOXA5 mRNA and increases its stability in response to RA treatment. Collectively, these results demonstrate that HuR and miR-130a dynamically regulate HOXA5 gene expression via modulating HOXA5 mRNA turnover and translation, respectively, thereby contributing to RA-induced growth inhibition. (C) 2013 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据