期刊
ONCOTARGET
卷 8, 期 38, 页码 63986-64000出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.19256
关键词
miR-195-5p; REG gamma; wnt/beta-catenin; renal cell carcinoma
资金
- National Natural Science Foundation of China [C050201, 81602216]
- Natural Science Foundation of Shanghai [16ZR1426500, 81401837, 81471066, 81261120555, 31200878, 31071875, 81271742]
- National Basic Research Program [2011CB504200, 2015CB910403]
- Science and Technology Commission of Shanghai Municipality [14430712100]
- Shanghai natural science foundation [12ZR1409300]
Renal cell carcinoma (RCC) is the most prevalent malignancy of kidney and accounts for approximately 4% of all cancer diagnoses in adults. Previous studies demonstrated microRNA-195-5p (miR-195-5p) as a tumor suppressor which is deregulated in many human cancers. However, the role of miR-195-5p in RCC is largely unknown. In the present study, we demonstrated that miR-195-5p was downregulated and negatively correlated with advanced clinical stage in RCC. Overexpression of miR-195-5p significantly suppressed RCC cells growth in vitro and in vivo, induced apoptosis and enhanced chemosensitivity to sorafenib. Conversely, suppression of miR-195-5p exhibited a reverse effect. REG gamma, a proteasome activator, was identified as a novel downstream target of miR-195-5p in RCC. Knockdown of REG gamma inhibited proliferation, induced apoptosis, increased sorafenib chemosensitivity and suppressed the wnt/beta-catenin pathway in RCC cells. Moreover, restoration of REG gamma markedly abolished the effects of miR-195-5p in RCC, and the wnt/beta-catenin pathway was suppressed by miR-195-5p overexpression while activated by miR-1955p inhibition in RCC cells. Our findings suggest that miR-195-5p is critical in REG gamma-mediated regulation of wnt/beta-catenin pathway in RCC development and may serve as a novel target for RCC treatment.
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