Helicobacter pylori virulence factors expression affect epigenetic factors leading to gastrointestinal carcinoma

Abstract

Disruption in the epigenetic mechanisms is one of the causes of cancer; particularly in the gut. It has been elucidated that multiple genetic and epigenetic alterations during this process caused by chronic inflammation play a crucial role in the cancer progress. DNA methylation impairment as a leading change is caused during the proliferation of Helicobacter pylori. It has been unraveled that numerous tumor suppressor genes are regulated by related promoter methylation, justifying environmental factors inducing gastric carcinoma. H. pylori infection affects various cells through inflammation, changes in apoptosis, proliferation and differentiation of epithelial cells into oncogenic cells. This is exerted through intracellular pathways in epithelial cells such as mitogen-activated protein kinase, Nuclear factor κB, activator protein, Wnt/β-catenin, Phosphoinositide 3-kinase pathways, signal transducers and transcriptional activators. The accumulations of cytosine methylation free radicals damage the DNA; hence nitric oxide (NO) alters the DNA-methylating enzymes function. Accordingly, gastritis due to H. pylori infection results in the inflammation and triggers signaling pathways mostly inducing gastrointestinal cancer. Noticeably, H. pylori-induced microRNAs exert epigenetic changes influencing various processes most of which including immune responses, autophagy, cell cycle and apoptosis. These mechanisms also stimulate gastric cancer progress. It is noteworthy that gene expression regulation through epigenetic mechanisms, including DNA methylation and micro-RNAs include major cellular pathways regulators. These epigenetic alterations represent prominent candidates for describing environmental factors roles in the genomic and cellular function enhancing the gastrointestinal carcinoma by H. pylori.