title: Retinoic acid-induced HOXA5 expression is co-regulated by HuR and miR-130a.
abstract: 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, a c-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.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Miao
authors.forename: Yide
authors.initials: Y
authors.lastname: Mei
authors.forename: Mian
authors.initials: M
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis / Q000187:drug effects; D060565:Argonaute Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051959:ELAV Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D020413:3' Untranslated Regions; C466422:AGO2 protein, human; D060565:Argonaute Proteins; D051959:ELAV Proteins; C489213:HOXA5 protein, human; D018398:Homeodomain Proteins; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014212:Tretinoin