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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer

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Manoel-Caetano, Fernanda S. [1] ; Rossi, Ana Flavia T. [1] ; de Morais, Gabriela Calvet [1] ; Severino, Fabio Eduardo [2] ; Silva, Ana Elizabete [1]
Total Authors: 5
[1] Sao Paulo State Univ, UNESP, Dept Biol, Campus Sao Jose do Rio Preto, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[2] Sao Paulo State Univ, UNESP, Fac Med, Dept Surg & Orthoped, Campus Botucatu, BR-18618687 Botucatu, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: GENES & DISEASES; v. 6, n. 2, p. 176-184, JUN 2019.
Web of Science Citations: 0

Gastric cancer remains one of the leading causes of cancer-related death worldwide, and most of the cases are associated with Helicobacter pylori infection. This bacterium promotes the production of reactive oxygen species (ROS), which cause DNA damage in gastric epithelial cells. In this study, we evaluated the expression of important genes involved in the recognition of DNA damage (ATM, ATR, and H2AX) and ROS-induced damage repair (APE1) and the expression of some miRNAs (miR-15a, miR-21, miR-24, miR-421 and miR-605) that target genes involved in the DNA damage response (DDR) in 31 fresh tissues of gastric cancer. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network. Analysis performed by real-time quantitative PCR exhibited significantly increased levels of the APE1 (RQ = 2.55, p < 0.0001) and H2AX (RQ = 2.88, p = 0.0002) genes beyond the miR-421 and miR-605 in the gastric cancer samples. In addition, significantly elevated levels of miR-21, miR-24 and miR-421 were observed in diffuse-type gastric cancer. Correlation analysis reinforced some of the gene:gene (ATM/ATR/H2AX) and miRNA:mRNA relationships obtained also with the interaction network. Thus, our findings show that tumor cells from gastric cancer presents deregulation of genes and miRNAs that participate in the recognition and repair of DNA damage, which could confer an advantage to cell survival and proliferation in the tumor microenvironment. Copyright (C) 2019, Chongqing Medical University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( (AU)

FAPESP's process: 15/21464-0 - Evaluation of effect of inflammaton on mediators in the signaling pathway TNF-a, on DNA damage response and interaction with network miRNAs in gastric carcinogenesis
Grantee:Ana Elizabete Silva
Support type: Regular Research Grants