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

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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.

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Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

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Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

Kenneth Livak, Thomas D. Schmittgen (2001)

The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).

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N6-Methyladenosine in Nuclear RNA is a Major Substrate of the Obesity-Associated FTO

Guifang Jia, Ye Fu, Xu Zhao … (2011)

We report here that FTO (fat mass and obesity-associated protein) exhibits efficient oxidative demethylation activity of abundant N 6-methyladenosine (m6A) residues in RNA in vitro. FTO knockdown with siRNA led to an increased level of m6A in mRNA, whereas overexpression of FTO resulted in a decreased level of m6A in human cells. We further show that FTO partially colocalizes with nuclear speckles, supporting m6A in nuclear RNA as a physiological substrate of FTO.

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Author and article information

Journal

Journal ID (nlm-ta): Oncol Lett

Journal ID (iso-abbrev): Oncol Lett

Journal ID (publisher-id): OL

Title: Oncology Letters

Publisher: D.A. Spandidos

ISSN (Print): 1792-1074

ISSN (Electronic): 1792-1082

Publication date Collection: April 2023

Publication date (Electronic): 28 February 2023

Publication date PMC-release: 28 February 2023

Volume: 25

Issue: 4

Electronic Location Identifier: 143

Affiliations

[1 ]Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education and Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China

[2 ]Hepatitis Laboratory, Department of Infectious Diseases, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China

[3 ]School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China

Author notes

Correspondence to: Professor Yuan Xie or Professor Jianjiang Zhou, Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education and Key Laboratory of Molecular Biology, Guizhou Medical University, 4 Beijing Road, Guiyang, Guizhou 550004, P.R. China, E-mail: 37408126qq.com jianjiangzhou@ 123456sina.cn

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Publisher ID: OL-25-4-13729

DOI: 10.3892/ol.2023.13729

PMC ID: 9996366

PubMed ID: 36909372

SO-VID: d71c5a71-2e74-4275-a4a4-fafd036bf3f6

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

History

Date received : 25 August 2022

Date accepted : 09 February 2023

Funding

Funded by: The National Natural Science Foundation of China

Award ID: 31960028

Award ID: 32160166

Funded by: The Key Project of Science and Technology of Guizhou Province

Award ID: (2020)1Z010

Funded by: The Science and Technology of Guizhou Province

Award ID: (2020)1Y333

This work was supported by The National Natural Science Foundation of China (grant nos. 31960028 and 32160166), The Key Project of Science and Technology of Guizhou Province [grant no. (2020)1Z010] and The Science and Technology of Guizhou Province [grant no. (2020)1Y333].

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

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Karger: Oncology

Most cited references 41

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

N6-Methyladenosine in Nuclear RNA is a Major Substrate of the Obesity-Associated FTO

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