A survival-related competitive endogenous RNA (ceRNA) network of lncRNAs, miRNAs and mRNAs associated with gastric cancer

Gastric cancer (GC) is known as a highly aggressive malignancy in which environmental and genetic factors can influence its development . Among the genetic factors, competitive endogenous (ce) RNAs can cross-regulate each other through the sequestrating of shared miRNAs and a↵ect the development of cancer . Purpose:In the present study, we investigate the relation of ceRNA elements with GC by construction of a competitive network based on RNA-seq data in The Cancer Genome Atlas.Methods:The RNA-seq and clinical data of GC patients were downloaded using TCGAbiolinks R-package , including ۳۳۵ tumor and ۳۰ non-tumor samples. Di↵erentially-expressed long non-coding RNAs (lncRNAs) (DELs), miRNAs (DEmiRs), and mRNAs (DEMs) were extracted by R-package DESeq۲ based on | Log۲Fold Change| >۱ and adjusted p<۰.۰۵. To screen the key survival-related DELs, DEmiRs, and DEMs, univariate Cox regression analysis was performed with a threshold of p<۰.۰۵. The multiMiR R-package and DIANA-LncBase v۳.۰ were used to predict the miRNA–mRNA and miRNA–lncRNA interactions. A lncRNA-miRNA-mRNA ceRNA network was then constructed and enrichment analysis was conducted for them using the Enrichr tool .Results:We identified ۳۹۴۷ DELs, ۲۶۶ DEmiRs, and ۴۳۸۸ DEMs, of these, ۱۸۷ DELs, ۲۴ DEmiRs, and ۵۲۴ DEMs were associated with the overall survival of GC patients. By integrating the relations with common miRNAs, we constructed a ceRNA network consisting of ۱۲ DELs, ۱۱ DEmiRs, and ۷۰ mRNAs. Our results revealed that these genes were significantly enriched in cancer-related pathways, including Pathways in cancer, HIF-۱, Hippo and p۵۳ signaling pathways. Conclusion:These results might help characterize the pathogenesis of GC and provide possibilities of introducing ceRNAs as diagnostic biomarkers or therapeutic targets.

کلیدواژه ها:

Gene Expression Profiling ، Non-coding RNAs ، Stomach neoplasms ، Systems Biology