miR-93-3p inhibition suppresses clear cell renal cell carcinoma proliferation, metastasis and invasion
Author(s) -
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,
Petr Glybochko,
Wanhai Xu
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.20458
Subject(s) - clear cell renal cell carcinoma , medicine , cancer research , cell growth , renal cell carcinoma , metastasis , downregulation and upregulation , oncology , cancer , biology , gene , genetics
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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