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Abstract
Gene expression is regulated at the transcription and translation levels; thus, both transcription factors (TFs) and microRNAs (miRNA) play roles in regulation of gene expression. This study profiled differentially expressed mRNAs and miRNAs in gastric cancer tissues to construct a TF and miRNA co-regulatory network in order to identify altered genes in gastric cancer progression. A total of 70 cases gastric cancer and paired adjacent normal tissues were subjected to cDNA and miRNA microarray analyses. We obtained 887 up-regulated and 93 down-regulated genes and 41 down-regulated and 4 up-regulated miRNAs in gastric cancer tissues. Using the Transcriptional Regulatory Element Database, we obtained 105 genes that are regulated by the E2F family of genes and using Targetscan, miRanda, miRDB and miRWalk tools, we predicted potential targeting genes of these 45 miRNAs. We then built up the E2F-related TF and miRNA co-regulatory gene network and identified 9 hub-genes. Furthermore, we found that levels of E2F1, 2, 3, 4, 5, and 7 mRNAs associated with gastric cancer cell invasion capacity, and has associated with tumor differentiation. These data showed Overexpression of E2F mRNAs associated with gastric cancer progression.
Highlights
Gastric cancer is still one of the most significant health problems in developing countries, like in China, its incidence is gradually decreasing in the Western countries
E2F family members play a major role during cell cycle G1/S transition in cells and the gene expression of E2F1, 2, 3, 4, 5, and 7 were all found to be overexpression (p < 0.01) in gastric cancer in this study
We utilized a cut-off value of 1.5 fold change to profiled differentially expressed mRNAs and miRNAs in gastric cancer tissues, which is consistent with most of previous study of cDNA or miRNA microarrays [19]. These differentially expressed mRNAs and miRNAs in gastric cancer tissues were mostly related to cell cycle progression, especially E2F family
Summary
Gastric cancer is still one of the most significant health problems in developing countries, like in China, its incidence is gradually decreasing in the Western countries. Gastric cancer is accounts for the fourth of incidence and the second of mortality rates among all cancers in the world [1–3]. Gastric cancer risk factors include Helicobacter pylori infection, frequent consumption of smoked foods, salted fish and meat, and pickled vegetables, tobacco smoke, obesity, or chronic gastritis. These risk factors could coordinate to manipulate gene expression or mutation or epigenetic alterations and eventually result in gastric cancer development. A large body of PLOS ONE | DOI:10.1371/journal.pone.0116979. A large body of PLOS ONE | DOI:10.1371/journal.pone.0116979 February 3, 2015
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