Evidence has shown that miRNAs can be regulated by multiple mechanisms and can participate in tumorigenesis and progression through binding to 3'-UTRs of target mRNAs. The present study identified differentially expressed miRNAs, mRNAs, and TFs by analyzing miRNA-Seq and mRNA-Seq data to construct a TFs/miRNAs/mRNAs regulation network for GC. We found five miRNAs (miR-18a-5p, miR-21-5p, miR-96-5p, miR-182-5p, and miR-196b-5p) that were significantly overexpressed in GC tissues. Clinical analyses indicated that higher miR-21-5p expression was associated with T3 + T4 and stage III + IV. The expression of miR-96-5p, miR-182-5p, and miR-196b-5p were positively correlated with the patients' ages. The five miRNAs had diagnostic efficacy in distinguishing GC from normal tissues. The gene interaction network showed that the five miRNAs were transcriptionally regulated by 11 TFs and negatively regulated 53 mRNA expressions through binding to the 3'-UTRs. Biological pathway analysis suggested that these TFs and target genes were involved in the p53 pathway, epithelial-to-mesenchymal transition, ErbB receptor, mTOR, VEGF, and VEGFR signaling networks. KEGG pathway analysis indicated that these genes were enriched in some cancer-associated pathways, including in GC. The five miRNAs may act as potential diagnostic markers and the TFs/miRNAs/mRNAs network could suggest a regulation mechanism of miRNAs.
Keywords: Diagnosis; Gastric cancer; Signaling pathway; Transcription factor; miRNA.
Copyright © 2020 Elsevier Inc. All rights reserved.