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镉在癌症中的表观遗传效应:以黑色素瘤为例。

Epigenetic effects of cadmium in cancer: focus on melanoma.

机构信息

Department of Experimental Specialistic Medical, Surgical and Odontostomatology Sciences, University of Messina, Messina, Italy.

Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

出版信息

Curr Genomics. 2014 Dec;15(6):420-35. doi: 10.2174/138920291506150106145932.

Abstract

Cadmium is a highly toxic heavy metal, which has a destroying impact on organs. Exposure to cadmium causes severe health problems to human beings due to its ubiquitous environmental presence and features of the pathologies associated with pro-longed exposure. Cadmium is a well-established carcinogen, although the underlying mechanisms have not been fully under-stood yet. Recently, there has been considerable interest in the impact of this environmental pollutant on the epigenome. Be-cause of the role of epigenetic alterations in regulating gene expression, there is a potential for the integration of cadmium-induced epigenetic alterations as critical elements in the cancer risk assessment process. Here, after a brief review of the ma-jor diseases related to cadmium exposure, we focus our interest on the carcinogenic potential of this heavy metal. Among the several proposed pathogenetic mechanisms, particular attention is given to epigenetic alterations, including changes in DNA methylation, histone modifications and non-coding RNA expression. We review evidence for a link between cadmium-induced epigenetic changes and cell transformation, with special emphasis on melanoma. DNA methylation, with reduced expression of key genes that regulate cell proliferation and apoptosis, has emerged as a possible cadmium-induced epigenetic mechanism in melanoma. A wider comprehension of mechanisms related to this common environmental contaminant would allow a better cancer risk evaluation.

摘要

镉是一种毒性很强的重金属,对人体器官有破坏作用。由于镉在环境中无处不在,且与长期接触相关的病理学特征有关,因此接触镉会对人类健康造成严重问题。镉是一种已被充分证实的致癌物质,尽管其潜在机制尚未完全被理解。最近,人们对这种环境污染物对表观基因组的影响产生了浓厚的兴趣。由于表观遗传改变在调节基因表达中的作用,镉诱导的表观遗传改变有可能作为癌症风险评估过程中的关键因素整合在一起。在这里,在简要回顾了与镉暴露相关的主要疾病之后,我们将重点放在这种重金属的致癌潜力上。在几种提出的发病机制中,特别关注表观遗传改变,包括 DNA 甲基化、组蛋白修饰和非编码 RNA 表达的改变。我们回顾了镉诱导的表观遗传变化与细胞转化之间的联系的证据,特别强调了黑色素瘤。DNA 甲基化,导致调节细胞增殖和凋亡的关键基因表达降低,已成为黑色素瘤中可能的镉诱导表观遗传机制。更广泛地了解与这种常见环境污染物相关的机制将有助于更好地评估癌症风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce13/4311387/b18aad2a8afb/CG-15-420_F1.jpg

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