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口腔鳞状细胞癌中的 DNA 甲基化:从其在致癌作用到潜在抑制剂药物的角色。

DNA methylation in oral squamous cell carcinoma: from its role in carcinogenesis to potential inhibitor drugs.

机构信息

Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.

Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.

出版信息

Crit Rev Oncol Hematol. 2021 Aug;164:103399. doi: 10.1016/j.critrevonc.2021.103399. Epub 2021 Jun 17.

Abstract

DNA methylation is one of epigenetic changes most frequently studied nowadays, together with its relationship with oral carcinogenesis. A group of enzymes is responsible for methylation process, known as DNA methyltransferases (DNMT). Although essential during embryogenesis, DNA methylation pattern alterations, including global hypomethylation or gene promoter hypermethylation, can be respectively associated with chromosomal instability and tumor suppressor gene silencing. Higher expression of DNA methyltransferases is a common finding in oral cancer and may contribute to inactivation of important tumor suppressor genes, influencing development, progression, metastasis, and prognosis of the tumor. To control these alterations, inhibitor drugs have been developed as a way to regulate DNMT overexpression, and they are intended to be associated with ongoing chemo- and radiotherapy in oral cancer treatments. In this article, we aimed to highlight the current knowledge about DNA methylation in oral cancer, including main hyper/hypomethylated genes, DNMT expression and its inhibitor treatments.

摘要

DNA 甲基化是目前研究最多的表观遗传改变之一,其与口腔癌发生的关系也备受关注。一组负责甲基化过程的酶被称为 DNA 甲基转移酶(DNMT)。虽然在胚胎发生过程中是必需的,但 DNA 甲基化模式的改变,包括全局低甲基化或基因启动子高甲基化,分别与染色体不稳定性和肿瘤抑制基因沉默相关。在口腔癌中,DNA 甲基转移酶的高表达是一种常见现象,可能导致重要肿瘤抑制基因失活,影响肿瘤的发生、进展、转移和预后。为了控制这些改变,已经开发出抑制剂药物来调节 DNMT 的过度表达,并打算将其与口腔癌的化疗和放疗联合应用。本文旨在强调口腔癌中 DNA 甲基化的最新知识,包括主要的高/低甲基化基因、DNMT 的表达及其抑制剂治疗。

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