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

// Shaojun Chen 1 , Longsheng Wang 1 , Xudong Yao 1 , Hui Chen 2 , Chen Xu 1 , Lu Tong 2 , Abdussaboor Shah 2 , Tingmei Huang 2 , Geng Chen 2 , Jiwei Chen 2 , Tie-Long Liu 3 , Xiao-Tao Li 2, 4 , Jun-Hua Zheng 1 and Lei Li 2 1 Department of Urology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, China 2 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China 3 Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China 4 Department of Molecular and Cellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA Correspondence to: Tie-Long Liu, email: czyyltl@163.com Xiao-Tao Li, email: xiaotaol@bcm.edu Jun-Hua Zheng, email: renalzjh@163.com Lei Li, email: lllkzj@163.com Keywords: miR-195-5p, REGγ, wnt/β-catenin, renal cell carcinoma Received: March 21, 2017     Accepted: June 12, 2017     Published: July 15, 2017 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.