Department of Urology/State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Medical School of Chinese PLA, Beijing, China.
PLoS One. 2013 Jul 5;8(7):e67758. doi: 10.1371/journal.pone.0067758. Print 2013.
Krüppel-like factor 4 (KLF4) is a transcription factor with diverse functions in various cancer types; however, the function of KLF4 in clear cell renal cell carcinoma (ccRCC) carcinogenesis remains unknown. In this study, we initially examined KLF4 expression by using a cohort of surgically removed ccRCC specimens and cell lines. Results indicated that the transcription and translation of KLF4 were lower in ccRCC tissues than in patient-matched normal tissues. Furthermore, the KLF4 expression was significantly downregulated in the five ccRCC cell lines at protein and mRNA levels compared with that in normal renal proximal tubular epithelial cell lines (HKC). KLF4 downregulation was significantly correlated with tumor stage and tumor diameter. Promoter hypermethylation may contribute to its low expression. In addition, in vitro studies indicated that the KLF4 overexpression significantly inhibited proliferation in human ccRCC cell lines 786-O and ACHN. Moreover, the KLF4 overexpression arrested the cell cycle progress at the G1/S phase transition by upregulating p21 (WAF1/CIP1) expression and downregulating cyclin D1 expression, KLF4 knockdown in HKC cells did the opposite. In vivo studies confirmed the anti-proliferative effect of KLF4. Our results suggested that KLF4 had an important function in suppressing the growth of ccRCC.
Krüppel 样因子 4（KLF4）是一种在多种癌症类型中具有多种功能的转录因子；然而，KLF4 在透明细胞肾细胞癌（ccRCC）发生中的作用尚不清楚。在这项研究中，我们最初使用手术切除的 ccRCC 标本和细胞系检查了 KLF4 的表达。结果表明，ccRCC 组织中的 KLF4 转录和翻译水平低于患者匹配的正常组织。此外，与正常肾近端肾小管上皮细胞系（HKC）相比，五种 ccRCC 细胞系在蛋白和 mRNA 水平上的 KLF4 表达均显著下调。KLF4 的下调与肿瘤分期和肿瘤直径显著相关。启动子超甲基化可能导致其低表达。此外，体外研究表明，KLF4 的过表达可显著抑制人 ccRCC 细胞系 786-O 和 ACHN 的增殖。此外，KLF4 的过表达通过上调 p21（WAF1/CIP1）的表达和下调细胞周期蛋白 D1 的表达，将细胞周期进程阻滞在 G1/S 期转换，而 KLF4 在 HKC 细胞中的敲低则起到相反的作用。体内研究证实了 KLF4 的抗增殖作用。我们的结果表明，KLF4 在抑制 ccRCC 的生长中具有重要功能。
