Chromatin and noncoding RNA-mediated mechanisms of gastric tumorigenesis

Sep 24, 2026

Chromatin and noncoding RNA-mediated mechanisms of gastric tumorigenesis are reviewed, focusing on how epigenetic regulators are frequently altered in gastric cancer. The article connects environmental influences—radiation, smoking, diet, and infectious pathogens—with epigenetic processes including DNA methylation and histone modifications. It highlights recent discoveries on histone modifiers and noncoding RNAs and explains how their interactions shape tumorigenesis. Improved insight is positioned to support development of novel targeted therapies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Histone modification and the chromatin landscape in gastric cancer

[www.nature.com/emm](www.nature.com/emm) REVIEW ARTICLE OPEN Chromatin and noncoding RNA-mediated mechanisms of gastric tumorigenesis Adrian Kwan Ho Loe 1,2,3, Lexin Zhu1,2,3 and Tae-Hee Kim 1,2 ✉ © The Author(s) 2023 | | | | | --- | --- | --- | | | Gastric cancer (GC) is one of the most common and deadly cancers in the world. It is a multifactorial disease highly inﬂuenced by environmental factors, which include radiation, smoking, diet, and infectious pathogens. Accumulating evidence suggests that epigenetic regulators are frequently altered in GC, playing critical roles in gastric tumorigenesis. Epigenetic regulation involves DNA methylation, histone modiﬁcation, and noncoding RNAs. While it is known that environmental factors cause widespread alterationsin DNA methylation, promoting carcinogenesis, the chromatin-and noncoding RNA-mediated mechanisms of gastric tumorigenesis are still poorly understood. In this review, we focus on discussing recent discoveries addressing the roles of histone modiﬁers and noncoding RNAs and the mechanisms of their interactions in gastric tumorigenesis. A better understanding of epigenetic | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | regulation would likely facilitate the development of novel therapeutic approaches targeting speciﬁc epigenetic regulators in GC. | | | | | Experimental & Molecular Medicine (2023) 55:22–31; [https://doi.org/10.1038/s12276-023-00926-0](https://doi.org/10.1038/s12276-023-00926-0) | | | | | | INTRODUCTION Gastric cancer (GC) is the ﬁfth most common cancer and the fourth deadliest cancer in the world1. GC shows distinct incidence patterns across geographical regions: most gastric cancer cases are found in Eastern Asia and Europe, while it is the most common cancer in some of Middle Eastern countries. Although the overall incidence and mortality have decreased in most countries, likely due to better prevention and improved food preservation, increasing incidence rates among young adult populations have been observed in some countries, such as the UK and Sweden2. Notably, the treatment of advanced or metastatic GC, with a median overall survival of less than one year, has been extremely challenging3. Therefore, a better understanding of the disease mechanisms would likely help design more effective therapies. Consistent with its distinct geographical distribution patterns, GC is a highly multifactorial disease regulated by genetic, epigenetic, and environmental factors. Common genetic factors include mutations in oncogenes and tumor suppressor genes involved in cancer initiation and progression4. The Cancer Genome Atlas (TCGA) project has identiﬁed common mutations and categorized GC into four major subtypes: Epstein‒Barr virus (EBV)-positive, microsatellite instability (MSI), genomically stable (GS), and chromosomal instability (CIN)5. Epigenetic factors are involved in the regulation of gene expression via mechanisms unrelated to the genetic sequence, which include DNA methylation, histone modiﬁcation, and noncoding RNAs (ncRNAs)6. Interestingly, analysis of tumor suppressors and oncogenes has shown that changes in DNA methylation are more common than genetic mutations in GC, highlighting the importance of epigenetic regulation in gastric tumorigenesis7. Corroborating these data, another study showed that the impact of DNA methylation outweighs that of genetic mutations in GC when compared to esophageal cancer8. Similarly, environmental factors, most notably diet and infection, play major roles in gastric carcinogenesis. In fact, GC is strongly associated with two infectious agents categorized as type I carcinogens, H. pylori and EBV9–13. Environmental and epigenetic factors are interconnected, as both diet and infection have been found to inﬂuence DNA methylation14, 15. While DNA methylation in GC has been extensively reviewed6, 16–18, other types of epigenetic regulation in GC are still poorly u

FAQs

Why are epigenetic regulators important in gastric cancer tumorigenesis?

Epigenetic regulators are frequently altered in gastric cancer and play critical roles in tumorigenesis, affecting gene expression through mechanisms such as DNA methylation, histone modification, and noncoding RNAs.

How do environmental factors relate to epigenetic changes in gastric cancer?

Environmental factors like diet and infection influence DNA methylation, linking external exposures to widespread epigenetic alterations that can promote carcinogenesis.

What is emphasized about histone modifiers and noncoding RNAs in this review?

The review discusses recent findings on the roles of histone modifiers and noncoding RNAs and clarifies the mechanisms of their interactions in gastric tumorigenesis.

Sep 24, 2026

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