Zhang Hai, Huang Chang-Jun, Tian Yuan, Wang Yu-Ping, Han Ze-Guang, Li Xiang-Cheng
Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Shanghai, China.
Asian Pac J Cancer Prev. 2012;13(11):5799-804. doi: 10.7314/apjcp.2012.13.11.5799.
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.
家族序列相似性189成员B（FAM189B），别名COTE1，是一种通过微阵列筛选出的假定癌基因，首次被发现在肝细胞癌（HCC）标本和HCC细胞系中显著上调。通过逆转录聚合酶链反应（RT-PCR）和实时定量PCR检测HCC样本和细胞系中COTE1的mRNA表达，同时通过免疫组织化学评估HCC组织中COTE1的蛋白表达。此外，在过表达或沉默COTE1后观察HCC细胞的侵袭情况。在总共48对HCC标本中，与相邻的非癌组织相比，31对标本中COTE1的表达上调（p<0.01）。在HCC细胞系中，COTE1的表达显著高于正常成人肝脏（p<0.01）。COTE1的过表达增强了HCC来源的LM6和MHCC-L细胞在体外的侵袭能力。相反，如在LM3和MHCC-H HCC细胞中所记录的，通过RNA干扰敲低COTE1显著抑制了这些表型。机制分析表明，COTE1可与肿瘤抑制因子WW结构域氧化还原酶（WWOX）发生物理结合。COTE1可能与肝细胞癌（HCC）细胞的侵袭密切相关，因此可能成为基因治疗的有效靶点。
