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肝癌发生的表观遗传学研究的当前进展。

Current progress in epigenetic research for hepatocarcinomagenesis.

作者信息

Huang Jian

机构信息

National Human Genome Research Center at Shanghai-Ministry of Science and Technology to build a healthy and disease Genomics Laboratory, Shanghai, 201203, China.

出版信息

Sci China C Life Sci. 2009 Jan;52(1):31-42. doi: 10.1007/s11427-009-0014-7. Epub 2009 Jan 19.

Abstract

Hepatocellular carcinoma is the main type of primary liver cancer, and also one of the most malignant tumors. At present, the pathogenesis mechanisms of liver cancer are not entirely clear. It has been shown that inactivation of tumor suppressor genes and activation of oncogenes play a significant role in carcinogenesis, caused by the genetic and epigenetic aberrance. In the past, people generally thought that genetic mutation is a key event of tumor pathogenesis, and somatic mutation of tumor suppressor genes is in particular closely associated with oncogenesis. With deeper understanding of tumors in recent years, increasing evidence has shown that epigenetic silencing of those genes, as a result of aberrant hypermethylation of CpG islands in promoters and histone modification, is essential to carcinogenesis and metastasis. The term epigenetics refers to heritable changes in gene expression caused by regulation mechanisms, other than changes in the underlying DNA sequence. Specific epigenetic processes include DNA methylation, genome imprinting, chromotin remodeling, histone modification and microRNA regulations. This paper reviews recent epigenetics research progress in the hepatocellular carcinoma study, and tries to depict the relationships between hepatocellular carcinomagenesis and DNA methylation as well as microRNA regulation.

摘要

肝细胞癌是原发性肝癌的主要类型,也是最恶性的肿瘤之一。目前,肝癌的发病机制尚不完全清楚。研究表明,抑癌基因失活和癌基因激活在由遗传和表观遗传异常引起的致癌过程中起重要作用。过去,人们普遍认为基因突变是肿瘤发病的关键事件,尤其是肿瘤抑制基因的体细胞突变与肿瘤发生密切相关。近年来,随着对肿瘤的深入了解,越来越多的证据表明,由于启动子区域CpG岛异常高甲基化和组蛋白修饰导致的这些基因的表观遗传沉默对肿瘤发生和转移至关重要。表观遗传学是指由调控机制引起的基因表达的可遗传变化,而不是指潜在DNA序列的变化。具体的表观遗传过程包括DNA甲基化、基因组印记、染色质重塑、组蛋白修饰和微小RNA调控。本文综述了近年来肝细胞癌研究中的表观遗传学进展,并试图阐述肝细胞癌发生与DNA甲基化以及微小RNA调控之间的关系。

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