title: OCT4 increases BIRC5 and CCND1 expression and promotes cancer progression in hepatocellular carcinoma.
abstract: BACKGROUND
  OCT4 and BIRC5 are preferentially expressed in human cancer cells and mediate cancer cell survival and tumor maintenance. However, the molecular mechanism that regulates OCT4 and BIRC5 expression is not well characterized.
  
  
  METHODS
  By manipulating OCT4 and BIRC5 expression in hepatocellular carcinoma (HCC) cell lines, the regulatory mechanism of OCT4 on BIRC5 and CCND1 were investigated.
  
  
  RESULTS
  Increasing or decreasing OCT4 expression could enhance or suppress BIRC5 expression, respectively, by regulating the activity of BIRC5 promoter. Because there is no binding site for OCT4 within BIRC5 promoter, the effect of OCT4 on BIRC5 promoter is indirect. An octamer motif for OCT4 in the CCND1 promoter has directly and partly participated in the regulation of CCND1 promoter activity, suggesting that OCT4 also could upregulated the expression of CCND1. Co-suppression of OCT4 and BIRC5 induced cancer cell apoptosis and cell cycle arrest, thereby efficiently inhibiting the proliferative activity of cancer cells and suppressing the growth of HCC xenogrfts in nude mice.
  
  
  CONCLUSIONS
  OCT4 can upregulate BIRC5 and CCND1 expression by increasing their promoter activity. These factors collusively promotes HCC cell proliferation, and co-suppression of OCT4 and BIRC5 is potentially beneficial for HCC treatment.
authors: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & Institute, Second Military Medical University, 200438, Shanghai, China.
authors: Lu
authors: L
authors: Cao
authors: Chunguang
authors: C
authors: Li
authors: Shuwen
authors: S
authors: Shen
authors: Yan
authors: Y
authors: Yan
authors: Weidan
authors: W
authors: Ji
authors: Jinghan
authors: J
authors: Wang
authors: Haihua
authors: H
authors: Qian
authors: Xiaoqing
authors: X
authors: Jiang
authors: Zhigang
authors: Z
authors: Li
authors: Mengchao
authors: M
authors: Wu
authors: Ying
authors: Y
authors: Zhang
authors: Changqing
authors: C
authors: Su
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000502:physiology; D019938:Cyclin D1 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000502:physiology*; D011401:Promoter Regions, Genetic; D000077022:Survivin; D015854:Up-Regulation
chemical_list: C107489:BIRC5 protein, human; C530104:CCND1 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; D000077022:Survivin; D019938:Cyclin D1