Journal
ONCOTARGET
Volume 7, Issue 45, Pages 73888-73902Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.12516
Keywords
renal cell carcinoma; miR-28-5p; RAP1B; proliferation; migration
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Funding
- National Basic Research Program of China [2014CB 542300]
- National Natural Science Foundation of China [81472021, 81401257, 81672102]
- Natural Science Foundation of Jiangsu Province [BK20140730]
- Foundation of Jinling Hospital [2014043]
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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.
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