Zbtb7 suppresses the expression of CDK2 and E2F4 in liver cancer cells: implications for the role of Zbtb7 in cell cycle regulation.

Zbtb7, a member of the POK protein family, is involved in tumorigenesis and cellular differentiation by acting as a crucial transcription factor, but its role in cell cycle modulation remains uncharacterized. In the present study, CDK2 and E2F4, two cell cycle regulators, are shown to be downregulated at the mRNA and protein levels by Zbtb7 in HepG2 and QGY7703 cells. Moreover, we demonstrate that the activities of CDK2 and E2F4 promoters were suppressed by the modulation of Zbtb7 levels and that Zbtb7 represses promoter activities through a mechanism involving direct binding of Zbtb7 to the promoters. Furthermore, it was identified that the site at -259 to -252 within the CDK2 promoter is responsible for Zbtb7-induced repression of the promoter activity. It was found that siRNA‑induced knockdown of Zbtb7 resulted in the suppression of cell cycle progression in HepG2 and QGY7703 cells. Collectively, these data indicate that CDK2 and E2F4 are the downstream targets of Zbtb7, and Zbtb7 may be a cell cycle modulator by regulating the expression of cell cycle-associated genes in liver cancer cells.