Insulin upregulates the expression of zinc finger and BTB domain-containing 7A in HepG2 cells

Zinc finger and BTB domain-containing 7A (Zbtb7A) is a proto-oncogene overexpressed in numerous cancers. In this study, we explored the mechanism of insulin-induced Zbtb7A expression. Real-time PCR and western blotting were used to detect Zbtb7A expression. Zbtb7A promoter activity was monitored by Luciferase reporter assay. It was shown that insulin elevates the mRNA and protein levels of the Zbtb7A gene in HepG2 cells. Using chemical inhibitors of insulin downstream pathways, we demonstrated that the insulin-induced Zbtb7A gene expression was completely blocked by LY294002, a PI3K/AKT inhibitor, and partially attenuated by the MAPK inhibitor PD98059. Transfection of HepG2 cells with a 1 kb Zbtb7A promoter-luciferase reporter construct revealed a dose-dependent activation of the Zbtb7A promoter by insulin, while mutation of the Sp1 binding site within the Zbtb7A promoter resulted in the failure of insulin-induced promoter activation, suggesting that insulin increases Zbtb7A expression through transcriptional regulation mediated by Sp1 in HepG2 cells.