Cholesterol promotes the migration and invasion of renal carcinoma cells by regulating the KLF5/miR-27a/FBXW7 pathway

Cholesterol promotes the migration and invasion of renal carcinoma cells by regulating the KLF5/miR-27a/FBXW7 pathway
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DOI:
10.1016/j.bbrc.2018.05.122
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发表时间:
2018-07-07
影响因子:
3.1
通讯作者:
Cao, Qingwei
Cao, Qingwei
中科院分区:
生物学4区
文献类型:
--
作者:
Liu, Zheng;Liu, Xiaowen;Cao, Qingwei

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透明细胞肾细胞癌(ccRCC)是肾细胞癌中最常见和最致命的亚型。胆固醇和胆固醇酯的积累是ccRCC的显著特征。然而,胆固醇对ccRCC的影响仍然未知。结果表明,胆固醇处理显著促进ccRCC中细胞的迁移和侵袭。机制分析表明胆固醇诱导KLF 5表达。KLF 5正调控miR-27 a的转录,增加miR-27 a的表达。MiR-27 a通过结合FBXW 7的3 'UTR直接靶向FBXW 7,降低FBXW 7的表达。FBXW 7基因沉默可进一步增加KLF 5和miR-27 a的表达,促进细胞的迁移和侵袭。提示胆固醇通过调节KLF 5/ miR-27 a/FBXW 7轴促进ccRCC细胞的迁移和侵袭。(C)2018由Elsevier Inc.出版
Clear cell renal cell carcinoma (ccRCC) is the most common and lethal subtype of renal cell carcinoma. Accumulation of cholesterol and cholesterol ester is a remarkable feature of ccRCC. However, the effect of cholesterol on ccRCC remains unknown. Out results showed that cholesterol treatment significantly promoted cells migration and invasion in ccRCC. Mechanism analysis indicated that cholesterol induced KLF5 expression. KLF5 positively regulated the transcription of miR-27a, increasing miR-27a expression. MiR-27a directly targeted FBXW7 by binding to its 3'UTR, reducing FBXW7 expression. FBXW7 silencing further increased the expression of KLF5 and miR-27a, and promoted cells migration and invasion. These results suggested that cholesterol accelerated ccRCC cells migration and invasion by regulating KLF5/ miR-27a/FBXW7 axis. (C) 2018 Published by Elsevier Inc.