Retinoic acid-induced HOXA5 expression is co-regulated by HuR and miR-130a

•Post-transcriptional regulation is indispensable for RA-induced HOXA5 expression.•miR130a/RISC relief from HOXA5 mRNA is required for RA-induced HOXA5 expression.•c-Myc directly regulates miR130a expression.•HuR is required for RA-induced HOXA5 expression.•HOXA5 expression regulated by miR-130a and HuR contributes to RA-induced cell death.

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.

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