Xu Pei-wei, Jin Yong-tang
Department of Environmental Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2013 Feb;30(1):70-3. doi: 10.3760/cma.j.issn.1003-9406.2013.01.017.
Lung cancer and chronic obstructive pulmonary disease (COPD) are the leading causes of morbidity and mortality worldwide. Development of lung cancer involves both genetic and environment factors. In addition to genetic alterations, epigenetic mechanism is closely involved in pathogenesis of lung cancer. Characterized by an abnormal persistent inflammatory response to noxious environmental stimulation, COPD has shown to increase the susceptibility for lung tumorigenesis in previous research. Current research on epigenetics of lung cancer and COPD has focused on aberrant DNA methylation, histone acetylation and non-coding RNAs regulation. The aberrant DNA methylation associated with lung cancer and COPD has included overexpression of DNA methyltransferase, global DNA hypomethylation and DNA hypermethylation in promoter regions, while histone acetylation and histone methylation are the major changes for histone modification, in which histone acetyltransferases, histone deacetylases, histone methyltransferases and histone demethylases play the most important roles. RNA interference and microRNAs are both hot topics of research on non-coding RNAs regulation. Understanding of concurrent epigenetic alterations in the pathogenesis of lung cancer and COPD may facilitate identification of specific therapeutic targets and development of effective treatment.
肺癌和慢性阻塞性肺疾病(COPD)是全球发病和死亡的主要原因。肺癌的发生涉及遗传和环境因素。除了基因改变外,表观遗传机制也密切参与肺癌的发病过程。COPD的特征是对有害环境刺激产生异常持续的炎症反应,先前的研究表明它会增加肺癌发生的易感性。目前关于肺癌和COPD表观遗传学的研究集中在异常的DNA甲基化、组蛋白乙酰化和非编码RNA调控。与肺癌和COPD相关的异常DNA甲基化包括DNA甲基转移酶的过表达、全基因组DNA低甲基化以及启动子区域的DNA高甲基化,而组蛋白乙酰化和组蛋白甲基化是组蛋白修饰的主要变化,其中组蛋白乙酰转移酶、组蛋白去乙酰化酶、组蛋白甲基转移酶和组蛋白去甲基化酶起着最重要的作用。RNA干扰和微小RNA都是非编码RNA调控研究的热点。了解肺癌和COPD发病机制中同时存在的表观遗传改变可能有助于确定特定的治疗靶点并开发有效的治疗方法。