The Anti-tumor Role And Mechanism Of MiR-503in Prostate Cancer

Prostate cancer is the second most prevalent cancer in men worldwide and the sixth leading cause of death in men, with its increasing incidence rate in China. Even with multiple treatment options such as hormone therapy, radiotherapy and chemotherapy, and surgery, patients still suffer from high rates of disease progression. MicroRNAs are a class of small-noncoding RNA capable of negatively regulating the gene expression. In this study, we focused on a rarely mentioned miRNA-miR-503, and studied its function in prostate cancer cells.1) MiR-503was quantified in human prostate cancer cells PC-3and DU-145by qPCR. Compared with the normal prostate epithelial cell line RWPE-1, the mean miR-503expression level in cancer cells was significantly low. However, CCND1and TLN1were up-regulated in PC-3and DU-145.2) To better understand miR-503’s function in prostate cancer cells, we conducted gain of function analysis by transfecting prostate cancer cells with chemically synthesized miR-503mimic. We found that over expression of miR-503could induce G1-phase arrest, and subsequently inhibit cells growth and colony formation in PC-3and DU-145. At72h after transfected with50nM miR-503, there was a reduction of cell viability of36%and38%in PC-3and DU-145cells respectively. Also, the colony formation ability was impared with a36%and19%drop respectively. However, no effect on cell apoptosis was detected. Morever, the cell migration and invasion were also significantly inhibited, which was validated by Transwell assay. Therefore, it was evident that miR-503functions as an anti-proliferation and anti-motility miRNA in prostate cancer;3) Finally, we investigated the mechanism of miR-503’s regulation on cell cycle arrest and motility. Using bioinformatic tool and florescent reporter system assay, we pinpointed the targeting genes CCND1and TLN1, which act as oncogenes in many other cancers. The RNA interference and overexpression study further supported the conclusion:miR-503suppresses proliferation and motility of prostate cancer cells by targeting cyclin D1and TLN1.In conclusion, we identified that miR-503was novel tumor suppressor microRNA in prostate cancer. It could suppress prostate caner cells growth via cell cycle arrest induction by targeting CCND1, and abrogate the migration and invasion capabilities of prostate cancer cells by targeting TLN1.