Krüppel-like transcription factor 8 regulates VEGFA expression in hepatocellular carcinoma through PI3K/Akt signal pathway
10.3781/j.issn.1000-7431.2014.11.486
- Author:
Sa-Nuo CHENG
1
Author Information
1. Department of Oncology, First Affiliated Hospital, Chongqing Medical University
- Publication Type:Journal Article
- Keywords:
Carcinoma, hepatocellular;
Krüppel-like transcription factors;
Neovascularization, pathologic;
Vascular endothelial growth factor A
- From:
Tumor
2014;34(12):1075-1081
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the regulating effect of Krüppel-like transcription factor 8 (KLF8) on the expression of vascular endothelial growth factor A (VEGFA) in hepatocellular carcinoma (HCC) and its potential mechanism. Methods: The expressions of KLF8 and VEGFA proteins and their correlation in paired HCC and adjacent paracancerous tissues were detected by immunohistochemistry staining. The KLF8 expression plasmid pcDNA3.1-KLF8 and the control plasmid were transfected into HCC SMMC7721 cells, respectively. The expressions of VEGFA and phosphoinositide-3-kinase (PI3K)/Akt pathway-related molecules including phospho-Akt (p-Akt), phospho-phosphoinositide-dependent kinase 1 (p-PDK1) and phospho-phosphatase and tensin homolog deleted on chromosome 10 (p-PTEN) in SMMC7721 cells were detected by real-time fluorescent quantitative PCR and Western blotting. The effect of PI3K/Akt pathway inhibitor LY294002 on the expression of VEGFA protein in SMMC7721 cells with KLF8 overexpression was detected by Western blotting. Chicken chorioallantoic membrane (CAM) model was used to detect the inducing effect of SMMC7721 cells with up-regulation of KLF8 expression on angiogenesis in chicken embryos. Results: The expression levels of KLF8 and VEGFA proteins were much higher in HCC tissues than those in the adjacent paracancerous tissues (P < 0.01). KLF8 protein expression was positively correlated with VEGFA protein expression in HCC tissues (r = 0.622, P < 0.01). The expression levels of KLF8, VEGFA, p-Akt, p-PDK1 and p-PTEN proteins were up-regulated in SMMC7721 cells transfected with pcDNA3.1-KLF8 plasmids (P < 0.05). LY294002 inhibited VEGFA expression in SMMC7721 cells with KLF8 overexpression (P < 0.05). The SMMC7721 cells with KLF8 overexpression had a higher potential in inducing angiogenesis in chick embryos (P < 0.01). Conclusion: KLF8 gene induces VEGFA expression and angiogenesis in HCC via PI3K/Akt signal pathway.
