title: Zbtb7 suppresses the expression of CDK2 and E2F4 in liver cancer cells: implications for the role of Zbtb7 in cell cycle regulation.
abstract: 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.
authors.affiliation: Nanhuan Hospital, University of South China, Hengyang, Hunan, People's Republic of China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Yang
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zu
authors.forename: Jing
authors.initials: J
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D050704:E2F4 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; D034741:RNA, Small Interfering; D014157:Transcription Factors; C485514:ZBTB7A protein, human; D051357:Cyclin-Dependent Kinase 2