MicroRNA­34a­5p serves as a tumor suppressor by regulating the cell motility of bladder cancer cells through matrix metalloproteinase­2 silencing.

ABSTRACT

Bladder cancer (BC), a common urologic cancer, is the fifth most frequently diagnosed tumor worldwide. hsa­miR­34a displays antitumor activity in several types of cancer. However, the functional mechanisms underlying hsa­miR­34a in BC remains largely unknown. We observed that hsa­mir­34a 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 hsa­miR­34a inhibited cell migration and invasion in BC cell lines 5637 and UMUC3 as detected by Transwell assays. We further found that hsa­miR­34a inhibited cell migration and invasion by silencing matrix metalloproteinase­2 (MMP­2) expression and thus interrupting MMP­2­mediated cell motility. Our analysis of BC datasets from The Cancer Genome Atlas database revealed a negative correlation between hsa­miR­34a and MMP­2. Moreover, higher MMP­2 protein expression was observed in the BC tissues when compared with that noted in the normal tissue. MMP­2 levels were also significantly associated with clinical disease stage and poor survival rate in human BC. These findings indicate that MMP­2 plays a critical role in regulating BC progression. Therefore, hsa­miR­34a is a promising treatment to target MMP­2 for the prevention and inhibition of cell migration and invasion in BC.