Posttranscriptional Regulation of Human Antigen R by miR-133b Enhances Docetaxel Cytotoxicity Through the Inhibition of ATP-Binding Cassette Subfamily G Member 2 in Prostate Cancer Cells.

Abstract

Docetaxel (DTX)-based chemotherapy is a first-line therapy in patients with castration-resistant prostate cancer. However, development of DTX resistance remains a challenge in cancer treatment. miRNAs have been shown to be involved in drug resistance in tumors. Nevertheless, little is known about the function and detailed molecular mechanism of miR-133b in DTX resistance of prostate cancer cells. The current study showed that miR-133b was downregulated, while human antigen R (HuR) was upregulated in prostate cancer cells. HuR was identified as a target of miR-133b, and miR-133b could suppress HuR expression. Ectopic expression of miR-133b and HuR knockdown suppressed cell viability and promoted DTX-induced apoptosis in DTX-treated prostate cancer cells, which were restored by HuR overexpression. Furthermore, HuR overexpression partially abolished the inhibitory effect of miR-133b overexpression on ATP-binding cassette (ABC) subfamily G member 2 (ABCG2) expression in prostate cancer cells. ABCG2 overexpression relieved DTX and miR-133b cytotoxicity in prostate cancer cells. In conclusion, posttranscriptional regulation of HuR by miR-133b enhances DTX cytotoxicity through inhibition of ABCG2, revealing a novel miR-133b/HuR/ABCG2 regulatory pathway to overcome chemoresistance in prostate cancer cells.