Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, PR China.
Department of Center Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
Biochem Biophys Res Commun. 2018 Jul 7;502(1):69-75. doi: 10.1016/j.bbrc.2018.05.122. Epub 2018 May 23.
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.
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 的一个显著特征。然而，胆固醇对 ccRCC 的影响尚不清楚。我们的结果表明，胆固醇处理显著促进了 ccRCC 细胞的迁移和侵袭。机制分析表明，胆固醇诱导 KLF5 的表达。KLF5 正向调节 miR-27a 的转录，增加 miR-27a 的表达。miR-27a 通过结合其 3'UTR 直接靶向 FBXW7，降低 FBXW7 的表达。FBXW7 的沉默进一步增加了 KLF5 和 miR-27a 的表达，并促进了细胞的迁移和侵袭。这些结果表明，胆固醇通过调节 KLF5/miR-27a/FBXW7 轴加速 ccRCC 细胞的迁移和侵袭。
