miR-28-5p acts as a tumor suppressor in renal cell carcinoma for multiple antitumor effects by targeting RAP1B

The incidence and mortality rate of renal cell carcinoma (RCC) have been significantly increasing; however, the mechanisms involved in RCC development and progression are unclear. In this study, we found that miR-28-5p was decreased in RCC tumor specimens and several renal carcinoma cell lines. By u...

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Bibliographic Details
Published in:Oncotarget 2016-11, Vol.7 (45), p.73888-73902
Main Authors: Wang, Cheng, Wu, Caiyun, Yang, Qi, Ding, Meng, Zhong, Jinsha, Zhang, Chen-Yu, Ge, Jingping, Wang, Junjun, Zhang, Chunni
Format: Article
Language:English
Subjects:
Animals
Carcinoma, Renal Cell - genetics
Carcinoma, Renal Cell - metabolism
Carcinoma, Renal Cell - pathology
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation - genetics
Disease Models, Animal
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Heterografts
Humans
Kidney Neoplasms - genetics
Kidney Neoplasms - metabolism
Kidney Neoplasms - pathology
Male
MAP Kinase Signaling System
Mice
MicroRNAs - genetics
Phosphorylation
rap GTP-Binding Proteins - genetics
Research Paper
RNA Interference
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Summary:The incidence and mortality rate of renal cell carcinoma (RCC) have been significantly increasing; however, the mechanisms involved in RCC development and progression are unclear. In this study, we found that miR-28-5p was decreased in RCC tumor specimens and several renal carcinoma cell lines. By using a combination of luciferase reporter assays and western blotting, we identified RAP1B, a Ras-related small GTP-binding oncoprotein implicated in a variety of tumors, as a direct target of miR-28-5p in RCC. The RAP1B protein level was increased in RCC tumor specimens and renal carcinoma cell lines, and this was inversely correlated with miR-28-5p expression. In vitro gain-of-function and loss-of-function studies in human renal carcinoma cell lines, demonstrated that miR-28-5p suppressed cell proliferation and migration by directly inhibiting RAP1B, and this effect was reversed by co-transfection with RAP1B. In addition, the stable overexpression of miR-28-5p inhibited tumor cell proliferation in vivo. This newly identified miR-28-5p/RAP1B axis provides a novel mechanism for the pathogenesis of RCC, and molecules in this axis may serve as potential biomarkers and therapeutic targets for RCC.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.12516