Experimental Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
Gastroenterology. 2010 Dec;139(6):2146-2157.e12. doi: 10.1053/j.gastro.2010.08.004. Epub 2010 Aug 19.
BACKGROUND & AIMS: The transcription factor Krüppel-like factor 8 (KLF8) has a role in tumor development, growth, and metastasis, but its role in hepatocellular carcinoma (HCC) is not clear.
KLF8 expression in human HCC cell lines and tumor tissues was measured by quantitative real-time polymerase chain reaction, immunoblot, and immunochemical analyses. The effects of KLF8 depletion or overexpression in HCC cells were observed in cultured cells and in mice. Changes in gene expression patterns in HCC cells in which levels of KLF8 were reduced using small interfering RNA were investigated by microarray analysis. The clinical significance of KLF8 expression levels were validated using tissue microarray analysis of surgical samples from 314 HCC patients.
KLF8 was overexpressed in highly metastatic HCC cell lines and in samples from patients with recurrent HCC. In cultured cells, KLF8 up-regulation promoted cell proliferation and invasion; inhibited apoptosis; down-regulated N-cadherin, vimentin, and fibronectin; and up-regulated E-cadherin. In mice, overexpression of KLF8 increased HCC progression and metastasis. Microarray analysis showed that reduction of KLF8 in HCC cells down-regulated expression of multiple genes involved in tumor progression and metastasis. KLF8 expression was a significant predictor of overall survival (P = .040) and time to HCC recurrence (P = .006) and was associated with early tumor recurrence (P = .001).
KLF8 promotes HCC cell proliferation and invasion, inhibits apoptosis, and induces the epithelial-to-mesenchymal transition. KLF8 up-regulation might be used to indicate poor prognosis or early recurrence of cancer in patients who have had surgery for HCC.
转录因子 Krüppel 样因子 8（KLF8）在肿瘤的发生、生长和转移中起作用，但它在肝细胞癌（HCC）中的作用尚不清楚。
通过定量实时聚合酶链反应、免疫印迹和免疫化学分析测量人 HCC 细胞系和肿瘤组织中的 KLF8 表达。观察 HCC 细胞中 KLF8 耗竭或过表达对培养细胞和小鼠的影响。使用小干扰 RNA 降低 HCC 细胞中 KLF8 水平，通过微阵列分析研究基因表达谱的变化。使用 314 例 HCC 手术样本的组织微阵列分析验证 KLF8 表达水平的临床意义。
KLF8 在高转移性 HCC 细胞系和复发性 HCC 患者的样本中过表达。在培养的细胞中，KLF8 的上调促进了细胞增殖和侵袭；抑制细胞凋亡；下调 N-钙黏蛋白、波形蛋白和纤维连接蛋白；上调 E-钙黏蛋白。在小鼠中，KLF8 的过表达增加了 HCC 的进展和转移。微阵列分析显示，HCC 细胞中 KLF8 的减少下调了多个参与肿瘤进展和转移的基因的表达。KLF8 的表达是总生存期（P =.040）和 HCC 复发时间（P =.006）的显著预测因子，与早期肿瘤复发相关（P =.001）。
KLF8 促进 HCC 细胞增殖和侵袭，抑制细胞凋亡，并诱导上皮-间充质转化。KLF8 的上调可能用于指示接受 HCC 手术的患者预后不良或癌症早期复发。
