Salt-driven chromatin remodeling associated with senescence dysregulation plays a crucial role in the carcinogenesis of gastric cancer subtype

IF 3.1 Q2 TOXICOLOGY Computational Toxicology Pub Date : 2023-02-01 DOI:10.1016/j.comtox.2023.100262
Karthik Balakrishnan
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引用次数: 2

Abstract

Many studies previously reported that salt (NaCl) at high concentrations has genotoxicity and carcinogenicity features in human cells. The current study used an integrative functional-genomics approach to identify the effect of high salt-driven dysregulation in gastric cancer subtype carcinogenesis. Therefore, gene sets related to salt, chromatin, and senescence were collected from the molecular signatures database and investigated their expression in the many gastric cancer mRNA expression profile cohorts and its cell lines profile using pathway-focused gene-sets activation scoring methods. In this study, high salt-induced chromatin remodeling associated with senescence-mediated dysregulation are exceedingly abundant in the intestinal subtype gastric tumors. This critical finding should pave the path for the targeted therapeutics treatment in the subtype of gastric tumors.

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与衰老失调相关的盐驱动染色质重塑在癌症亚型胃癌发生中起着至关重要的作用
许多研究报道了高浓度盐(NaCl)对人体细胞具有遗传毒性和致癌性。目前的研究使用综合功能基因组学方法来确定高盐驱动的失调在胃癌亚型癌变中的作用。因此,我们从分子特征数据库中收集了与盐、染色质和衰老相关的基因集,并使用途径聚焦的基因集激活评分方法研究了它们在许多胃癌mRNA表达谱队列及其细胞系谱中的表达。在本研究中,高盐诱导的与衰老介导的失调相关的染色质重塑在肠亚型胃肿瘤中非常丰富。这一重要发现将为胃癌亚型的靶向治疗铺平道路。
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来源期刊
Computational Toxicology
Computational Toxicology Computer Science-Computer Science Applications
CiteScore
5.50
自引率
0.00%
发文量
53
审稿时长
56 days
期刊介绍: Computational Toxicology is an international journal publishing computational approaches that assist in the toxicological evaluation of new and existing chemical substances assisting in their safety assessment. -All effects relating to human health and environmental toxicity and fate -Prediction of toxicity, metabolism, fate and physico-chemical properties -The development of models from read-across, (Q)SARs, PBPK, QIVIVE, Multi-Scale Models -Big Data in toxicology: integration, management, analysis -Implementation of models through AOPs, IATA, TTC -Regulatory acceptance of models: evaluation, verification and validation -From metals, to small organic molecules to nanoparticles -Pharmaceuticals, pesticides, foods, cosmetics, fine chemicals -Bringing together the views of industry, regulators, academia, NGOs
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