Gastrointestinal and liver diseases research center (GLDRC), Guilan University of Medical Sciences, Rasht, Iran.
Gastrointestinal and liver diseases research center (GLDRC), Guilan University of Medical Sciences, Rasht, Iran.
Biomed Pharmacother. 2019 Jan;109:144-156. doi: 10.1016/j.biopha.2018.10.094. Epub 2018 Nov 2.
Gastric cancer (GC) or human gastric adenocarcinoma is one of the most commonplace type of serious cancers and also the most common cause of cancer-related mortality in the world. Relatively, many studies have acknowledged that GC is a multi-factorial pathological situation that environmental factors, particularly dietary ones and H.pylori infection are considered to have a strong key role in the etiology of GC. Inappropriate dietary habits are the first cause as they affect main molecular functions related with the onset of the GC tumorigenesis and carcinogenesis. Correspondingly, cancer investigation has impressively zoomed on the different genetic markers and also molecular mechanisms pathways responsible for the progression of the GC. Various molecular signaling pathways such as WNT, NOTCH, SHH, MYC have different functions and analyzing their role in the GC is of great importance particularly for the treatment modalities. Proportionately, fluctuations of epigenetic alterations including DNA methylation, histone modification, histone acetylation and also histone phosphorylation's are involved in all cancers specially the GC. Conspicuously, novel developments in cancer epigenetic have indicated immense reprogramming of every structure of the epigenetic mechanism in cancer, comprising microRNAs, nucleosome positioning, DNA methylation, noncoding RNAs, and histone modifications. In this account, aberrant DNA methylation mechanism in the promoter regions of certain genes, which leads to silencing of some particular genes such as tumor suppressor and other cancer-related genes in carcinogenesis, is the most important epigenetic hallmark in human GC especially as a target for detection and diagnosis in cancer treatment. Here, we review the importance of epigenetic fluctuations alongside with their molecular signaling mechanism in the GC.
胃癌（GC）或人类胃腺癌是最常见的严重癌症之一，也是世界上癌症相关死亡率最高的癌症。相对而言，许多研究已经认识到 GC 是一种多因素的病理情况，环境因素，特别是饮食因素和 H.pylori 感染被认为在 GC 的病因中起关键作用。不适当的饮食习惯是首要原因，因为它们影响与 GC 肿瘤发生和癌变相关的主要分子功能。相应地，癌症研究引人注目地集中在不同的遗传标记和分子机制途径上，这些途径负责 GC 的进展。各种分子信号通路，如 WNT、NOTCH、SHH、MYC，具有不同的功能，分析它们在 GC 中的作用非常重要，特别是对治疗方式。相应地，表观遗传改变的波动包括 DNA 甲基化、组蛋白修饰、组蛋白乙酰化和组蛋白磷酸化，都参与了所有癌症，特别是 GC。值得注意的是，癌症表观遗传学的新发展表明，癌症表观遗传机制的每一个结构都发生了巨大的重编程，包括 microRNAs、核小体定位、DNA 甲基化、非编码 RNA 和组蛋白修饰。在本研究中，在某些基因的启动子区域中出现异常的 DNA 甲基化机制，导致某些特定基因（如肿瘤抑制基因和其他与癌症相关的基因）沉默，这是人类 GC 中最重要的表观遗传标志，特别是作为癌症治疗中检测和诊断的靶点。在这里，我们综述了表观遗传波动及其在 GC 中的分子信号机制的重要性。
