miR-93-3p inhibition suppresses clear cell renal cell carcinoma proliferation, metastasis and invasion

miR-93-3p 抑制可抑制透明细胞肾细胞癌的增殖、转移和侵袭

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作者:Lu Wang, Guang Yang, Xiangwei Zhu, Ziqi Wang, Hongzhi Wang, Yang Bai, Pengcheng Sun, Li Peng, Wei Wei, Guang Chen, Guangbin Li, Andrey A Zamyatnin Jr, Peter V Glybochko, Wanhai Xu

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.

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