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Ectopic Overexpression of COTE1 Promotes Cellular Invasion of Hepatocellular Carcinoma

  • Zhang, Hai (Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health) ;
  • Huang, Chang-Jun (Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health) ;
  • Tian, Yuan (Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health) ;
  • Wang, Yu-Ping (Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai) ;
  • Han, Ze-Guang (Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai) ;
  • Li, Xiang-Cheng (Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health)
  • Published : 2012.11.30

Abstract

Family with sequence similarity 189, member B (FAM189B), alias COTE1, a putative oncogene selected by microarray, for the first time was here found to be significantly up-regulated in hepatocellular carcinoma (HCC) specimens and HCC cell lines. mRNA expression of COTE1 in HCC samples and cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR, while protein expression of COTE1 in HCC tissues was assessed by immunohistochemistry. In addition, invasion of HCC cells was observed after overexpressing or silencing COTE1. In the total of 48 paired HCC specimens, compared with the adjacent non-cancer tissues, the expression of COTE1 was up-regulated in 31 (p<0.01). In HCC cell lines, COTE1 expression was significantly higher than in normal human adult liver (p<0.01). Overexpression of COTE1 enhanced HCC-derived LM6 and MHCC-L cellular invasion in vitro. In contrast, COTE1 knockdown via RNAi markedly suppressed these phenotypes, as documented in LM3 and MHCC-H HCC cells. Mechanistic analyses indicated that COTE1 could physically associate with WW domain oxidoreductase (WWOX), a tumor suppressor. COTE1 may be closely correlated with invasion of hepatocellular carcinoma (HCC) cells and thus may serve as an effective target for gene therapy.

Keywords

Acknowledgement

Supported by : National Natural Science Foundation

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