Journal
ONCOTARGET
Volume 8, Issue 47, Pages 82824-82834Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.20458
Keywords
ccRCC; miR-93-3p; PEDF; apoptosis; migration
Categories
Funding
- National Natural Science Foundation of China [81602225, 81572482, 81270022, 81611130070]
- Natural Science Foundation of Heilongjiang Province of China [QC2016120]
- Russian Foundation for Basic Research [165453115]
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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 epitheliumderived factor (PEDF). A direct PEDF-miR-93-3p interaction was confirmed via dualluciferase 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, miR93- 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 anticcRCC therapeutic target.
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