title: Exo70 is transcriptionally up-regulated by hepatic nuclear factor 4α and contributes to cell cycle control in hepatoma cells.
abstract: 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.
authors: Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.
authors: Yujie
authors: Y
authors: Zhao
authors: Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.
authors: Jihuan
authors: J
authors: Hou
authors: Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.
authors: Panying
authors: P
authors: Mi
authors: Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.
authors: Liyuan
authors: L
authors: Mao
authors: Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.
authors: Liang
authors: L
authors: Xu
authors: Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.
authors: Youyu
authors: Y
authors: Zhang
authors: Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.|Department of Oncology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen 361004, Fujian Province, PR China.
authors: Li
authors: L
authors: Xiao
authors: Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.
authors: Hanwei
authors: H
authors: Cao
authors: Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.
authors: Wenqing
authors: W
authors: Zhang
authors: Department of Basic Medicine, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.
authors: Bing
authors: B
authors: Zhang
authors: Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.
authors: Gang
authors: G
authors: Song
authors: Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.
authors: Tianhui
authors: T
authors: Hu
authors: Cancer Research Center, Xiamen University Medical College, Xiamen 361102, Fujian Province, PR China.
authors: Yan-yan
authors: YY
authors: Zhan
mesh_terms: D001599:Berberine / Q000494:pharmacology; D016203:CDC2 Protein Kinase; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D056945:Hep G2 Cells; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C547754:EXOC7 protein, human; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; D001599:Berberine; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases
keywords: Exo70; HNF4α; cell cycle regulation; hepatoma; transcription