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新型基因 FAM43B 的表达受肝癌细胞系中 DNA 甲基化的调控,该基因可抑制细胞增殖。

Expression of a novel gene FAM43B repressing cell proliferation is regulated by DNA methylation in hepatocellular carcinoma cell lines.

机构信息

National Human Genome Center, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui-Jin II Road, Shanghai 200025, China.

出版信息

Mol Cell Biochem. 2011 Aug;354(1-2):11-20. doi: 10.1007/s11010-011-0800-y. Epub 2011 Apr 2.

Abstract

The epigenetic dysregulation of tumor suppressor genes plays an important role in many cancers, including hepatocellular carcinoma (HCC). In this study, we identified a new gene, family with sequence similarity 43, member B (FAM43B), based on a previous genome-wide approach. FAM43B was significantly downregulated in 60% (24/40) HCC specimens as compared to non-HCC livers. Enforced FAM43B overexpression could suppress cell growth and colony formation in vitro, and induce cell cycle delay, whereas FAM43B knockdown enhanced cell growth. The expression level of FAM43B was found related to the methylation level of FAM43B promoter in HCC cell lines and HCC specimens. The collective data suggest that the expression of FAM43B was regulated by methylation and the epigenetic silencing of FAM43B could contribute to HCC tumorigenesis by regulating cell proliferation.

摘要

肿瘤抑制基因的表观遗传失调在许多癌症中发挥着重要作用,包括肝细胞癌(HCC)。在本研究中,我们通过之前的全基因组方法,鉴定了一个新基因,家族与序列相似性 43,成员 B(FAM43B)。与非 HCC 肝脏相比,FAM43B 在 60%(24/40)的 HCC 标本中显著下调。FAM43B 的过表达可抑制体外细胞生长和集落形成,诱导细胞周期延迟,而 FAM43B 的敲低则增强细胞生长。在 HCC 细胞系和 HCC 标本中发现 FAM43B 的表达水平与 FAM43B 启动子的甲基化水平有关。综合数据表明,FAM43B 的表达受甲基化调控,FAM43B 的表观遗传沉默可能通过调节细胞增殖促进 HCC 肿瘤发生。

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