Effects of Helicobacter pylori on the expression of the FTO gene and its biological role in gastric cancer

Abstract

Helicobacter pylori (Hp) is a primary risk factor for gastric cancer. The fat mass and obesity-associated (FTO) gene is associated with the development and progression of various cancer types such as glioma, leukemia, breast cancer and colorectal cancer. The aim of the present study was to investigate the effect of Hp infection on the expression of FTO and its roles in gastric cancer. It was found that the expression levels of both FTO mRNA and protein were significantly increased in Hp-infected human gastric mucosal epithelial cells and Mongolian gerbil gastric tissues. The expression of FTO in gastric cancer tissues was higher than that in para-cancer tissues. Data from The Cancer Genome Atlas demonstrated that FTO expression in gastric cancer tissues was significantly higher than that in normal tissues. Patient survival rate was significantly decreased in patients with high expression levels of FTO. It was also demonstrated that FTO expression was associated with several pathological parameters, such as tumor stage, metastasis stage and the American Joint Committee on Cancer stage. The FTO gene was positively correlated with 16,601 genes in gastric cancer and negatively correlated with 3,623 genes. Gene Ontology enrichment analysis demonstrated that FTO was significantly enriched in the regulation of gene expression and oxidative RNA demethylase activity, and it was associated with components such as the RNA N6-methyladenosine methyltransferase complex and nuclear speckle. In addition, knockdown of the FTO gene inhibited the migration and invasion of Hp-infected cells. In conclusion, the data suggests that Hp infection leads to upregulation of the FTO gene, which may be related to patient survival rate, tumor staging and other pathological parameters of patients with gastric cancer. It also suggests that FTO promotes proliferation and migration of gastric cancer cells, which may be involved in the pathogenesis of Hp-induced gastric cancer.

A Ferroptosis-Related lncRNAs Signature Predicts Prognosis of Colon Adenocarcinoma

“…In in vitro studies in nude mice, METTL3 knockdown was found to inhibit COAD migration and epithelial-mesenchymal transition (EMT) by inhibiting DDX27 expression [41]. FTO is highly expressed in gastric cancer and negatively correlated with patient survival [42]. FTO inhibitors in COAD can effectively inhibit the proliferation, invasion, and metastasis.…”

The bidirectional interplay between ncRNAs and methylation modifications in gastrointestinal tumors

“…FTO, on the other hand, is a demethylase that can remove m6A methylation modification on RNA molecules. FTO is overexpressed in various cancers and promotes biological processes such as tumor cell proliferation, angiogenesis, and drug resistance by reducing m6A levels [37][38][39].…”