原发性肝癌的表观遗传学及其治疗

doi:10.16288/j.yczz.14-443

遗传 ›› 2015, Vol. 37 ›› Issue (6): 517-527.doi: 10.16288/j.yczz.14-443

原发性肝癌的表观遗传学及其治疗

孙凌云^{1, 2}, 李星逾², 孙志为²

1. 昆明理工大学医学院, 昆明 650500;
2. 昆明理工大学附属医院肝胆外科,昆明 650032

收稿日期:2014-12-15 修回日期:2015-03-24 出版日期:2015-06-20 发布日期:2015-05-14
通讯作者: 孙志为,教授,研究方向：肝胆外科、微创外科、移植外科、消化道肿瘤。E-mail: 2833570686@qq.com
作者简介:孙凌云,硕士研究生,专业方向：分子靶向治疗肝细胞癌的临床及实验。E-mail: sly84@qq.com
基金资助:
云南省应用基础研究计划项目(编号：2012WS007)资助

Progress of epigenetics and its therapeutic application in hepatocellular carcinoma

Lingyun Sun^{1, 2}, Xingyu Li², Zhiwei Sun²

1. Medical College, Kunming University of Science and Technology, Kunming 650500, China;
2. Hepatobiliary Surgery, Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China

Received:2014-12-15 Revised:2015-03-24 Online:2015-06-20 Published:2015-05-14

摘要/Abstract

摘要： 肝癌是一种严重危害人类健康的恶性疾病,在全世界患癌人群中,肝癌的发生率排第五,死亡率排第二。原发性肝癌(Hepatocellular carcinoma, HCC)是最普遍的肝癌组织学亚型,属于异质性疾病,对其治疗涉及遗传学、基因组学、环境毒理学等多个领域。尽管许多分子靶向治疗药物如索拉菲尼等已经进入临床应用并证明有效,但细胞毒性等负效应不容忽视,目前迫切需要新的治疗靶点和药物高效并选择性的杀伤肝癌细胞。大量证据表明,肝脏肿瘤的发生和发展与表观遗传学密切相关,DNA甲基化、组蛋白修饰、miRNA表达的异常及表观遗传相关基因表达的异常都是HCC中显著的表观遗传异常现象。表观治疗药物可能会逆转异常基因的表达,从而使HCC的发生和发展得以控制。文章综述了HCC表观遗传学治疗方面的研究进展,展望了未来利用类似的疗法治疗肝癌的潜力。

关键词: 原发性肝癌, 表观遗传学, DNA甲基化, 组蛋白修饰, miRNA, lncRNA

Abstract: Liver cancer is a severe harmful disease. It is the fifth most frequently diagnosed cancer and second most frequent cause of cancer deaths worldwide. As the most popular histologic subtype of hepatocellular carcinoma (HCC), primary HCC is a heterogeneous disease whose management requires a multidisciplinary approach combining genetics, genomics and environmental toxicology. Although many molecular targeted therapies such as sorafenib have entered clinical application and proven effective, the cytotoxicity and other negative effects cannot be ignored. There is an urgent need to identify new therapeutic targets and drugs, which can kill HCC cells with high efficiency and specificity. Plenty of evidence suggests that occurrence and development of HCC is closely related with epigenetics. DNA methylation, histone modification, aberrant expression of miRNAs and dysregulated expression of many epigenetic regulatory genes are significantly altered in HCC. Epigenetic therapeutic drugs may reverse abnormal gene expression, thus controlling the occurrence and development of HCC. In this review, we summarize the latest research progresses in epigenetics and its therapeutic application in HCC,and the potential treatments to be used in the future.

Key words: hepatocellular carcinoma, epigenetics, DNA methylation, histone modification, miRNA, LncRNA

孙凌云, 李星逾, 孙志为. 原发性肝癌的表观遗传学及其治疗[J]. 遗传, 2015, 37(6): 517-527.

Lingyun Sun, Xingyu Li, Zhiwei Sun. Progress of epigenetics and its therapeutic application in hepatocellular carcinoma[J]. HEREDITAS(Beijing), 2015, 37(6): 517-527.

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原发性肝癌的表观遗传学及其治疗

Progress of epigenetics and its therapeutic application in hepatocellular carcinoma

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