Krüppel-Like Factor 8 Regulates VEGFA Expression In Hepatocellular Carcinoma By PI3K/Akt Signal Pathway

Objective:To investigate the regulating role of Kruppel-like factor 8 (KLF8) on vascular endothelial growth factor A (VEGFA) expression in hepatocellular carcinoma (HCC) and its potential molecular mechanism.Methods:Expression of KLF8 and VEGFA in paired HCC and adjacent tissues were detected by immunohistochemistry staining. KLF8 expression plasmid pcDNA3.1-KLF8 was transfected into HCC SMMC7721 cells to up-regulating KLF8 expression. The expressions of KLF8, VEGFA and phosphoinositide-3-kinase (PI3K)/Akt signal pathway involved proteins (p-Akt, p-PDK1, and p-PTEN) were detected by RT-qPCR and western blotting. Effect of PI3K/Akt pathway inhibitor LY294002 on expression of VEGFA protein in KLF8 up-regulated SMMC7721 cells was detected by western blotting. Chicken chorioallantoic membrane (CAM) model was used to detect the effect of KLF8 up-regulated SMMC7721 cells on inducing angiogenesis.Results:The expression level of KLF8 and VEGFA was higher in HCC tissues than that in adjacent normal tissues (P<0.01). KLF8 protein expression was highly correlated with VEGFA protein expression in HCC (r=0.622, P< 0.01). The expression level of KLF8, VEGFA, p-Akt, p-PDK1 and p-PTEN were up-regulated in SMMC7721 transfected with pCDNA3.1-KLF8 (P< 0.05). LY294002 inhibited VEGFA expression in KLF8 overexpressed SMMC7721 cells (P< 0.05). KLF8 up-regulated SMMC7721 cells had higher potential in inducing angiogenesis than the control cells(P< 0.01).Conclusion:KLF8 may induce VEGFA expression and angiogenesis in HCC by PI3K/Akt signal pathway.