Suppression of α-methylacyl-coenzyme A racemase by miR200c inhibits prostate adenocarcinoma cell proliferation and migration.

Overexpression of α-methylacyl-coenzyme A racemase (AMACR/P504S) is a major abnormality that has been observed in prostate cancer, whereas microRNA (miRNA/miR) 200c, is downregulated. The aim of the present study was to explore whether miR200c was able to exert any regulatory effects on AMACR. To meet this aim, bioinformatics analysis was performed to identify potential binding sites for miR200c in the 3'-untranslated region (3'-UTR) of AMACR. Recombinant adenoviral and dual reporter gene assays were designed to examine the binding of miR200c to the potential seed sequences in the AMACR 3'-UTR. Conventional reverse transcription (RT)-PCR, RT-quantitative (q)PCR and western blotting were also used to examine the regulatory effects of miR200c on AMACR at the mRNA and protein levels. Furthermore, Cell Counting Kit-8, wound healing and Transwell assays were performed to investigate the biological effects of miR200c-AMACR deregulation on prostate cancer cell proliferation, migration and invasion. It was revealed that miR200c post-transcriptionally suppressed AMACR expression by interacting with the 90-97 nucleotide sequence of the AMACR mRNA 3'-UTR. Artificial overexpression of miR200c significantly downregulated the mRNA and protein levels of AMACR in DU145 and PC-3 prostate cancer cells. Knockdown of AMACR by RNA interference, or overexpression of miR200c by recombinant adenoviral Ad-miR200c, inhibited prostate cancer cell proliferation, migration and invasiveness. Taken together, the results of the present study revealed that miR200c may suppress the AMACR expression level post-transcriptionally. The results also indicate that perturbation of the miR200c-AMACR regulatory mechanism may be involved in prostate carcinogenesis and that this may be exploited in future therapeutic approaches to prostate cancer.