E2F8 contributes to human hepatocellular carcinoma via regulating cell proliferation.
The E2F family member of transcription factors includes the atypical member E2F8, which has been little studied in cancer. We report that E2F8 is strongly upregulated in human hepatocellular carcinoma (HCC), where it was evidenced to contribute to oncogenesis and progression. Ectopic overexpression of E2F8 promoted cell proliferation, colony formation, and tumorigenicity, whereas E2F8 knockdown inhibited these phenotypes, as documented in Huh-7, Focus, Hep3B, and YY-8103 HCC cell lines. Mechanistic analyses indicated that E2F8 could bind to regulatory elements of cyclin D1, regulating its transcription and promoting accumulation of S-phase cells. Together, our findings suggest that E2F8 contributes to the oncogenic potential of HCC and may constitute a potential therapeutic target in this disease.
Deng
Qing
Q
National Human Genome Center, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201203, China.
Wang
Qun
Q
Zong
Wei-Ying
WY
Zheng
Da-Li
DL
Wen
Yi-Xin
YX
Wang
Ke-Sheng
KS
Teng
Xiao-Mei
XM
Zhang
Xin
X
Huang
Jian
J
Han
Ze-Guang
ZG
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D016193:G1 Phase / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D016196:S Phase / Q000502:physiology; D014162:Transfection; D015854:Up-Regulation
C504723:E2F8 protein, human; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D019938:Cyclin D1