miR-145-Mediated Tumor Suppression in Bladder Urothelial Carcinoma via Targeting the ADAMTS5/Wnt Signaling Axis

Bladder urothelial carcinoma (BLCA) is the most common urological tumor with high mortality. The present study aimed to investigate the role of miR-145 in the tumorigenesis of BLCA.

The levels of miR-145 and ADAMTS5 were examined in BLCA specimens. BLCA cell lines T24 and 5637 were adopted for in vitro experiments. ADAMTS5 was verified as a downstream target of miR-145 using a luciferase reporter assay. Cell viability and apoptosis were detected using the CCK-8 assay and flow cytometry. Cell migratory and invasive capacities were examined by the transwell assay. The protein levels of ADAMTS5, E-cadherin, N-cadherin, and vimentin were analyzed by western blotting.

miR-145 was found to be negatively correlated to the expression of ADAMTS5 in BLCA specimens. ADAMTS5 was identified as a direct target of miR-145. In addition, PCR and western blotting showed that miR-145 overexpression reduced ADAMTS5 levels, suppressed cell viability, and induced cell apoptosis, whereas miR-145 knockdown triggered the opposite result. miR-145 has also been verified to impede epithelial-mesenchymal transition (EMT) activation in tumor progression.

The present study revealed that miR-145 negatively regulates the expression of ADAMTS5. This regulatory effect of miR-145 may be associated with the Wnt/β‑catenin signaling pathway. Therefore, miR-145 has the potential to be used as a biomarker for predicting the progression of BLCA.