Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer
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...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2019-06-01
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| Series: | Genes and Diseases |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304219300157 |
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| author | Fernanda S. Manoel-Caetano Ana Flávia T. Rossi Gabriela Calvet de Morais Fábio Eduardo Severino Ana Elizabete Silva |
| author_facet | Fernanda S. Manoel-Caetano Ana Flávia T. Rossi Gabriela Calvet de Morais Fábio Eduardo Severino Ana Elizabete Silva |
| author_sort | Fernanda S. Manoel-Caetano |
| collection | DOAJ |
| description | 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. Keywords: DNA damage response, DNA repair, Gastric cancer, Gene expression, microRNA |
| first_indexed | 2024-03-12T18:02:16Z |
| format | Article |
| id | doaj.art-37e3350c9b1443a99883551e53f46a85 |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T18:02:16Z |
| publishDate | 2019-06-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-37e3350c9b1443a99883551e53f46a852023-08-02T09:33:41ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422019-06-0162176184Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancerFernanda S. Manoel-Caetano0Ana Flávia T. Rossi1Gabriela Calvet de Morais2Fábio Eduardo Severino3Ana Elizabete Silva4Department of Biology, UNESP, São Paulo State University, Campus of São José do Rio Preto, Rua Cristóvão Colombo, 2265, 15.054-000, São José do Rio Preto, São Paulo, BrazilDepartment of Biology, UNESP, São Paulo State University, Campus of São José do Rio Preto, Rua Cristóvão Colombo, 2265, 15.054-000, São José do Rio Preto, São Paulo, BrazilDepartment of Biology, UNESP, São Paulo State University, Campus of São José do Rio Preto, Rua Cristóvão Colombo, 2265, 15.054-000, São José do Rio Preto, São Paulo, BrazilDepartment of Surgery and Orthopedics, Faculty of Medicine, UNESP, São Paulo State University, Campus of Botucatu, Av. Prof. Mário Rubens Guimarães Montenegro, s/n, 18.618-687, Botucatu, São Paulo, BrazilDepartment of Biology, UNESP, São Paulo State University, Campus of São José do Rio Preto, Rua Cristóvão Colombo, 2265, 15.054-000, São José do Rio Preto, São Paulo, Brazil; Corresponding author. Department of Biology, São Paulo State University (UNESP), Rua Cristóvão Colombo, 2265, São José do Rio Preto, 15054-000, SP, Brazil. Fax: +55 17 3221 2390.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. Keywords: DNA damage response, DNA repair, Gastric cancer, Gene expression, microRNAhttp://www.sciencedirect.com/science/article/pii/S2352304219300157 |
| spellingShingle | Fernanda S. Manoel-Caetano Ana Flávia T. Rossi Gabriela Calvet de Morais Fábio Eduardo Severino Ana Elizabete Silva Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer Genes and Diseases |
| title | Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer |
| title_full | Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer |
| title_fullStr | Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer |
| title_full_unstemmed | Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer |
| title_short | Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer |
| title_sort | upregulation of the ape1 and h2ax genes and mirnas involved in dna damage response and repair in gastric cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2352304219300157 |
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