Manoel-Caetano Fernanda S, Rossi Ana Flávia T, Calvet de Morais Gabriela, Severino Fábio Eduardo, Silva Ana Elizabete
Department 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.
Department 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, Brazil.
Genes Dis. 2019 Apr 5;6(2):176-184. doi: 10.1016/j.gendis.2019.03.007. eCollection 2019 Jun.
Gastric cancer remains one of the leading causes of cancer-related death worldwide, and most of the cases are associated with 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 (, , and ) and ROS-induced damage repair () 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 (RQ = 2.55, p < 0.0001) and (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 () 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.
胃癌仍然是全球癌症相关死亡的主要原因之一，并且大多数病例与感染有关。这种细菌促进活性氧（ROS）的产生，ROS会导致胃上皮细胞中的DNA损伤。在本研究中，我们评估了31例新鲜胃癌组织中参与DNA损伤识别（、和）和ROS诱导的损伤修复（）的重要基因的表达，以及一些靶向参与DNA损伤反应（DDR）基因的miRNA（miR-15a、miR-21、miR-24、miR-421和miR-605）的表达。使用Cytoscape v3.1.1构建推测的miRNA:mRNA相互作用网络。通过实时定量PCR进行的分析显示，在胃癌样本中，miR-421和miR-605之外的基因（RQ = 2.55，p < 0.0001）和（RQ = 2.88，p = 0.0002）的水平显著升高。此外，在弥漫型胃癌中观察到miR-21、miR-24和miR-421水平显著升高。相关性分析加强了一些通过相互作用网络也获得的基因:基因（）和miRNA:mRNA关系。因此，我们的研究结果表明，胃癌肿瘤细胞中参与DNA损伤识别和修复的基因和miRNA存在失调，这可能赋予肿瘤微环境中细胞存活和增殖的优势。
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