C1orf61 acts as a tumor activator in human hepatocellular carcinoma and is associated with tumorigenesis and metastasis
C1orf61 acts as a tumor activator in human hepatocellular carcinoma and is associated with tumorigenesis and metastasis
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C1orf61 在人肝细胞癌中充当肿瘤激活剂，与肿瘤发生和转移相关
DOI：
10.1096/fj.12-216622
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发表时间：
2013-01-01
期刊：
影响因子：
4.8
通讯作者：
Li, Wenhua
中科院分区：
文献类型：
--
作者：
Hu, Hai-Ming;Chen, Yicheng;Li, Wenhua
1q 染色体长臂（包含 C1orf61 的染色体区域）的基因组扩增是人类癌症中的常见事件。然而，1号染色体开放阅读框61（C1orf61）在肝细胞癌（HCC）中的表达模式及其对HCC进展的影响仍不清楚。我们之前曾报道过 C1orf61 在人类胚胎发生过程中高度上调。在这项研究中，我们报告 C1orf61 表达与肝病的进展相关。我们发现C1orf61在肝硬化组织中表达上调，并且在原发性HCC肿瘤中进一步表达上调。此外，乙型肝炎病毒（HBV）阳性患者的 C1orf61 表达水平显着高于 HBV 阴性患者。对高度恶性 HCC 细胞系的评估显示 C1orf61 蛋白表达水平较高。此外，发现 C1orf61 蛋白主要分布在细胞质内。 C1orf61 在非恶性 L02 细胞系中的异位表达促进了体外细胞增殖和集落形成，并通过调节特定细胞周期相关蛋白的表达来促进细胞周期进程。此外，L02细胞中C1orf61的过度表达促进细胞侵袭和转移。上皮标记物（E-钙粘蛋白和occludin）的下调和间质标记物（N-钙粘蛋白、波形蛋白和snail）的上调表明C1orf61的过度表达诱导了与转移相关的上皮-间质转化（EMT）。总之，我们的研究结果首次证明了 C1orf61 在 HCC 肿瘤发生和转移中的作用。-Hu, H-M., Chen, Y., Liu, L., Zhuang, C-C., Wang, W., Kong, K., Huang, Z.,Guo, M-X., Li, W-X., Li, W. C1orf61 在人类肝细胞癌中充当肿瘤激活剂，并与肿瘤发生和转移。 FASEB J. 27, 163–173 (2013)。 www.fasebj.org
The genomic amplification of chromosome 1q long arm, the chromosomal region containing C1orf61, is a common event in human cancers. However, the expression pattern of chromosome 1 open reading frame 61 (C1orf61) in hepatocellular carcinoma (HCC) and its effects on HCC progression remain unclear. We have previously reported that C1orf61 is highly up‐regulated during human embryogenesis. In this study, we report that C1orf61 expression is associated with the progression of liver disease. We found that C1orf61 is up‐regulated in hepatic cirrhosis tissues and is further up‐regulated in primary HCC tumors. Moreover, hepatitis B virus (HBV)‐positive patients exhibited significantly higher levels of C1orf61 expression than HBV‐negative patients. The evaluation of highly malignant HCC cell lines revealed high protein expression levels of C1orf61. Furthermore, the C1orf61 protein was found to be predominantly distributed within the cytoplasm. The ectopic expression of C1orf61 in the nonmalignant L02 cell line promoted cellular proliferation and colony formation in vitro, as well as cell cycle progression via the regulation of the expression of specific cell cycle‐related proteins. In addition, the overexpression of C1orf61 in L02 cells facilitated cellular invasion and metastasis. The down‐regulation of epithelial markers (E‐cadherin and occludin) and the up‐regulation of mesenchymal markers (N‐cadherin, vimentin, and snail) suggested that the overexpression of C1orf61 induced the epithelial‐mesenchymal transition (EMT) that is linked to metastasis. Taken together, our findings demonstrate, for the first time, the roles of C1orf61 in HCC tumorigenesis and metastasis.—Hu, H‐M., Chen, Y., Liu, L., Zhang, C‐C., Wang, W., Gong, K., Huang, Z., Guo, M‐X., Li, W‐X., Li, W. C1orf61 acts as a tumor activator in human hepatocellular carcinoma and is associated with tumorigenesis and metastasis. FASEB J. 27, 163–173 (2013). www.fasebj.org