MicroRNA-34a-5p serves as a tumor suppressor by regulating the cell motility of bladder cancer cells through matrix metalloproteinase-2 silencing

Bladder cancer (BC), a common urologic cancer, is the fifth most frequently diagnosed tumor worldwide. hsa-miR-34a displays antitumor activity in several types of cancer. However, the functional mechanisms underlying hsa-miR-34a in BC remains largely unknown. We observed that hsa-mir-34a levels were significantly and negatively associated with clinical disease stage as well as regional lymph node metastasis in human BC. In a series of in vitro investigations, overexpression of hsa-miR-34a inhibited cell migration and invasion in BC cell lines 5637 and UMUC3 as detected by Transwell assays. We further found that hsa-miR-34a inhibited cell migration and invasion by silencing matrix metalloproteinase-2 (MMP-2) expression and thus interrupting MMP-2-mediated cell motility. Our analysis of BC datasets from The Cancer Genome Atlas database revealed a negative correlation between hsa-miR-34a and MMP-2. Moreover, higher MMP-2 protein expression was observed in the BC tissues when compared with that noted in the normal tissue. MMP-2 levels were also significantly associated with clinical disease stage and poor survival rate in human BC. These findings indicate that MMP-2 plays a critical role in regulating BC progression. Therefore, hsa-miR-34a is a promising treatment to target MMP-2 for the prevention and inhibition of cell migration and invasion in BC.