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.
Keywords: bladder cancer; microRNA-34a-5p; migration; invasion; MMP-2.