microRNA-204 modulates chemosensitivity and apoptosis of prostate cancer cells by targeting zinc-finger E-box-binding homeobox 1 (ZEB1)

Epigenetic gene inactivation by microRNAs (miRNAs) is crucial in malignant transformation, prevention of apoptosis, development of drug resistance, and metastasis. miR-204 dysregulation has been reported in prostate cancer (PC). It is considered to exert tumor suppressor functions and is associated with the development of chemoresistance. However, the detailed mechanisms underlying the role of miR-204 in PC, particularly in chemoresistance, remain to be fully elucidated. In this study, analysis using miRNA microarray showed that miR-204 is downregulated in chemoresistant PC tissues with respect to its expression in chemosensitive PC tissues and benign prostatic hyperplasia tissues. Microarray results were validated via qPCR. The changes in miR-204 expression levels were also observed in vitro. Forced overexpression of miR-204 evidently attenuated docetaxel chemoresistance and promoted apoptosis in PC-3-R cells, whereas miR-204 knockdown effectively reduced docetaxel-induced cell death and inhibited cell apoptosis. Mechanistically, miR-204 directly targets the 3'-untranslated region of zinc-finger E-box-binding homeobox 1 (ZEB1) and inhibits its protein expression via translational repression. Furthermore, suppression of ZEB1 could effectively improve miR-204 deficiency-triggered chemoresistance in PC cells. Our results collectively indicate that miR-204 expression is downregulated in chemoresistant PC tissues and cells and that miR-204/ZEB1 could potentially be used as adjunct therapy for patients with advanced/chemoresistant PC.