Up-regulation of miR-181a in clear cell renal cell carcinoma is associated with lower KLF6 expression, enhanced cell proliferation, accelerated cell cycle transition, and diminished apoptosis
Up-regulation of miR-181a in clear cell renal cell carcinoma is associated with lower KLF6 expression, enhanced cell proliferation, accelerated cell cycle transition, and diminished apoptosis
复制标题
透明细胞肾细胞癌中 miR-181a 的上调与 KLF6 表达降低、细胞增殖增强、细胞周期转变加速和细胞凋亡减少相关
DOI：
10.1016/j.urolonc.2017.09.019
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发表时间：
2018-03-01
影响因子：
2.7
通讯作者：
Zhang, Xu
中科院分区：
文献类型：
--
作者：
Lei, Zhenwei;Ma, Xin;Zhang, Xu
目的：miR-181 a的异常表达伴随着许多人类肿瘤的发生。然而，在肾透明细胞癌（ccRCC）中，miR-181 a的作用仍不清楚。本研究的目的是研究miR-181 a的生物学功能及其在ccRCC组织和癌细胞系中的表达水平。来自42名患者的ccRCC肿瘤和邻近非肿瘤组织样品以及786-0，769-P，A498，和CAKI-1 ccRCC细胞系通过定量实时聚合酶链反应测定。使用生物信息学方法预测miR-181 a的潜在靶点，然后使用荧光素酶报告基因测定进行验证。结果：miR-181 a在肾细胞癌组织和细胞系中表达上调，miR-181 a在肾细胞癌细胞系中表达上调，miR-181 a在肾细胞癌细胞系中表达上调，miR-181 a在肾细胞癌细胞系中表达上调，miR-181 a在肾细胞癌细胞系中表达上调。miR-181 a的表达水平与肿瘤大小、肿瘤/淋巴结/转移分期、Fuhrman分级显著相关。荧光素酶分析显示KLF 6是miR-181 a的靶点。KLF 6表达与miR-181 a水平呈负相关。miR-181 a的过表达导致KLF 6 mRNA和蛋白水平降低，而KLF 6基因中潜在miR-181 a结合位点的突变消除了这种抑制作用。结论：miR-181 a在肾细胞癌中表达上调，可能通过靶向KLF 6的表达而发挥促癌作用。操纵miR-181 a可以在治疗ccRCC中提供有益效果。(c)2018爱思唯尔公司All rights reserved.
Objectives: Dysregulated expression of miR-181a accompanies tumorigenesis in many human cancers. However, in clear cell renal cell carcinoma (ccRCC), the role of miR-181a remains unclear. The aim of this study was to investigate biological functions of miR-181a and its expression levels in ccRCC tissues and cancer cell lines.Material and methods: Expression levels of miR-181a in samples of ccRCC tumors and adjacent nontumor tissues from 42 patients as well as in 786-0, 769-P, A498, and CAKI-1 ccRCC cell lines were determined by quantitative real-time polymerase chain reaction. Potential targets of miR-181a were predicted using bioinformatic approaches and then verified by using the luciferase reporter assay. The effects of miR-181a on cell proliferation, colony formation, cell cycle progression, and apoptosis were investigated in ccRCC cell lines transfected with specific miR-181a mimic and inhibitor.Results: We found that miR-181a expression was up-regulated in ccRCC tissues and cell lines. The expression level of miR-181a significantly correlated with the tumor size, tumor/node/metastasis staging, and Fuhrman grade. Luciferase assays showed that KLF6 was a target of miR-181a. KLF6 expression was inversely correlated with the level of miR-181a. Overexpression of miR-181a led to reduced KLF6 mRNA and protein levels, whereas mutations of the potential miR-181a binding sites in the KLF6 gene abrogated this inhibitory effect. Furthermore, overexpression of miR-181a promoted proliferation and Gl/S cell cycle transition, as well as inhibited apoptosis by down-regulating KLF6 in ccRCC cells.Conclusions: miR-181a is up-regulated in ccRCC and may act as a tumor promoting factor by targeting KLF6 expression. Manipulating miR-181a may provide a beneficial effect in the treatment of ccRCC. (c) 2018 Elsevier Inc. All rights reserved.