miR-195-5p is critical in REGγ-mediated regulation of wnt/β-catenin pathway in renal cell carcinoma
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Shaojun Chen1, Longsheng Wang1, Xudong Yao1, Hui Chen2, Chen Xu1, Lu Tong2, Abdussaboor Shah2, Tingmei Huang2, Geng Chen2, Jiwei Chen2, Tie-Long Liu3, Xiao-Tao Li2,4, Jun-Hua Zheng1 and Lei Li2
1Department of Urology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, China
2Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China
3Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China
4Department of Molecular and Cellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA
Tie-Long Liu, email: [email protected]
Xiao-Tao Li, email: [email protected]
Jun-Hua Zheng, email: [email protected]
Lei Li, email: [email protected]
Keywords: miR-195-5p, REGγ, wnt/β-catenin, renal cell carcinoma
Received: March 21, 2017 Accepted: June 12, 2017 Published: July 15, 2017
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.
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