miR-195-5p is critical in REGγ-mediated regulation of wnt/β- catenin pathway in renal cell carcinoma

Abstract

Renal cell carcinoma (RCC) is the most prevalent malignancy of kidney and accounts for approximately 4% of all cancer diagnoses in adults. Previous studies demonstrated microRNA-195-5p (miR-195-5p) as a tumor suppressor which is deregulated in many human cancers. However, the role of miR-195-5p in RCC is largely unknown. In the present study, we demonstrated that miR-195-5p was downregulated and negatively correlated with advanced clinical stage in RCC. Overexpression of miR-195-5p significantly suppressed RCC cells growth in vitro and in vivo, induced apoptosis and enhanced chemosensitivity to sorafenib. Conversely, suppression of miR-195-5p exhibited a reverse effect. REGγ, a proteasome activator, was identified as a novel downstream target of miR-195-5p in RCC. Knockdown of REGγ inhibited proliferation, induced apoptosis, increased sorafenib chemosensitivity and suppressed the wnt/β-catenin pathway in RCC cells. Moreover, restoration of REGγ markedly abolished the effects of miR-195-5p in RCC, and the wnt/β-catenin pathway was suppressed by miR-195-5p overexpression while activated by miR-195- 5p inhibition in RCC cells. Our findings suggest that miR-195-5p is critical in REGγ- mediated regulation of wnt/β-catenin pathway in RCC development and may serve as a novel target for RCC treatment.