Chromatin and noncoding RNA-mediated mechanisms of gastric tumorigenesis

Gastric cancer: Interplay of epigenetic regulatorsDetailed studies of epigenetic regulation in gastric cancer could provide novel targets for combination therapies. Gastric cancer development is heavily influenced by environmental factors such as diet, which drive epigenetic changes to DNA and gene expression. Tae-Hee Kim and colleagues at the Hospital for Sick Children in Toronto, Canada, reviewed current understanding of epigenetic regulation in gastric cancer, focusing on non-coding RNA and modifications to histones, proteins that bind to DNA. Histone modifications alter chromatin, the DNA and protein complexes that form chromosomes, and this directly influences gene expression. These modifications are reversible, involving specific 'writer' and 'eraser' proteins. In gastric cancer, dysregulation of writer and eraser proteins alters the expression of cancer-related genes, while non-coding RNAs regulate critical cancer-promoting pathways. Further investigations are needed into how non-coding RNAs and histone modifications interact. 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 alterations in 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.