Exo70 is transcriptionally up-regulated by hepatic nuclear factor 4α and contributes to cell cycle control in hepatoma cells
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Yujie Zhao1, Jihuan Hou1, Panying Mi1, Liyuan Mao1, Liang Xu1, Youyu Zhang1, Li Xiao1,2, Hanwei Cao1, Wenqing Zhang1, Bing Zhang3, Gang Song1, Tianhui Hu1, Yan-yan Zhan1
1Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China
2Department of Oncology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen 361004, Fujian Province, PR China
3Department of Basic Medicine, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China
Yan-yan Zhan, e-mail: firstname.lastname@example.org
Tianhui Hu, e-mail: email@example.com
Keywords: Exo70, HNF4α, transcription, cell cycle regulation, hepatoma
Received: August 26, 2015 Accepted: January 19, 2016 Published: February 02, 2016
Exo70, a member of the exocyst complex, is involved in cell exocytosis, migration, invasion and autophagy. However, the expression regulation and function of Exo70 in hepatocellular carcinoma are still poorly understood. In this study, we found Exo70 expression in human hepatoma cells was greatly reduced after knocking down hepatic nuclear factor 4α (HNF4α), the most important and abundant transcription factor in liver. This regulation occurred at the transcriptional level but not post-translational level. HNF4α transactivated Exo70 promoter through directly binding to the HNF4α-response element in this promoter. Cell cycle analysis further revealed that down-regulation of HNF4α and Exo70 was essential to berberine-stimulated G2/M cell cycle arrest in hepatoma cells. Moreover, knocking down either Exo70 or HNF4α induced G2/M phase arrest of hepatoma cells. Exo70 acted downstream of HNF4α to stimulate G2/M transition via increasing Cdc2 expression. Together, our results identify Exo70 as a novel transcriptional target of HNF4α to promote cell cycle progression in hepatoma, thus provide a basis for the development of therapeutic strategies for hepatocellular carcinoma.
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