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// Lu Wang 1, * , Guang Yang 2, * , Xiangwei Zhu 1 , Ziqi Wang 1 , Hongzhi Wang 1 , Yang Bai 1 , Pengcheng Sun 1 , Li Peng 1 , Wei Wei 1 , Guang Chen 1 , Guangbin Li 1 , Andrey A. Zamyatnin Jr 3, 4 , Peter V. Glybochko 3, 4 and Wanhai Xu 1 1 Department of Urology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang Province, P.R. China 2 Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, P.R. China 3 Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, Russia 4 A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia * These authors have contributed equally to this work Correspondence to: Wanhai Xu, email: xuwanhaia@163.com Keywords: ccRCC, miR-93-3p, PEDF, apoptosis, migration Received: January 02, 2017 Accepted: June 29, 2017 Published: August 24, 2017 ABSTRACT miRNA dysregulation is associated with many human diseases, including cancer. This study explored the effects of miR-93-3p on clear cell renal cell carcinoma (ccRCC). We found that miR-93-3p is upregulated an average of 38-fold in 138 ccRCC specimens compared to matched normal kidney tissues, which correlated with poor patient outcome. miR-93-3p inhibition reduced ccRCC cell growth, invasion, and migration in vitro and in a mouse xenograft model. A search of the TargetScan, miRanda, and PicTar databases revealed that miR-93-3p is predicted to regulate pigment epithelium-derived factor (PEDF). A direct PEDF-miR-93-3p interaction was confirmed via dual-luciferase reporter assays. Like miR-93-3p inhibition, PEDF overexpression induced cell apoptosis and inhibited migration and invasion. Additionally, co-transfection with PEDF siRNA reversed the effects of miR-93-3p inhibition in ccRCC cells. Thus, miR-93-3p is a likely ccRCC oncogene that acts by regulating PEDF. These results suggest that miR-93-3p may predict ccRCC patient clinical outcome and serve as a novel anti-ccRCC therapeutic target. |
