Construction of a circular RNA‐microRNA‐messengerRNA regulatory network in stomach adenocarcinoma

Abstract

Objectives Circular RNAs (circRNAs) can interact with microRNAs (miRNAs) to regulate gene expression in cancer cells. However, the roles of competitive endogenous RNA (ceRNA) networks consisting of differentially expressed circRNAs (DECs), miRNAs, and messenger RNAs (mRNAs) in stomach adenocarcinoma (STAD) remain unclear. This study was performed to explore novel regulatory networks in STAD. Methods The circRNA expression profiles, as well as miRNA and mRNA sequence data of STAD, were retrieved from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), respectively. Candidates were identified to construct a network through a comprehensive bioinformatics strategy. The expression of hub‐genes identified by protein‐protein interactions (PPI) was validated by quantitative reverse transcription (RT) polymerase chain reaction. Results A total of 51 DECs were identified in the GSE83521 and GSE89143 datasets of GEO. A total of 11 448 differentially expressed mRNAs (DEMs) and 458 differentially expressed miRNAs (DEMIs) were obtained by RNA sequencing of TCGA‐STAD. Prediction by using five online databases (Cancer‐Specific CircRNA, CircInteractome, miRTarBase, miRDB, and TargetScan) resulted in the selection of 6 DECs, 6 DEMIs, and 36 DEMs to establish a circRNA‐miRNA‐mRNA regulatory network based on the interactions of circRNA‐miRNA and miRNA‐mRNA. Through PPI analysis, four hub‐genes (COL10A1, COL5A2, COL4A1, and COL3A1) were discovered. Moreover, overexpressions of COL10A1, COL5A1, and COL4A1 were associated with a poor overall survival rate of patients with STAD. On the basis of TNM staging, we found that the expressions of COL10A1, COL5A2, and COL3A1 in T2, T3, and T4 was significantly higher than in T1. Hub‐genes expressions were validated in STAD tissues and cell lines. Conclusions Our study provides a novel perspective on the regulatory mechanism of STAD involving ceRNAs including DECs, DEMIs, and DEMs.

Comprehensive Analysis of a circRNA-miRNA-mRNA Network to Reveal Potential Inflammation-Related Targets for Gastric Adenocarcinoma

“…Compared with the study by Gu et al [ 3 ], which showed that the p53 signalling pathway and the Hippo signalling pathway were significantly enriched in GC, while the KEGG results indicated that the ECM-receptor interaction pathway might be involved in the development of GC in this study. Meanwhile, the results are consistent with the previous study [ 33 ]. The ECM-receptor interaction pathway has been identified in multiple cancers, and it includes “cell adhesion molecules (CAMs)” and “cell cycle” pathways [ 34 ].…”

Derivation and Validation of a Prognostic Model for Cancer Dependency Genes Based on CRISPR-Cas9 in Gastric Adenocarcinoma

“…But limitations of the present study are not to be neglected. Firstly, despite the fact that TCGA database has been widely used in various aspects of researches ( 41 , 42 ), some important preoperative and postoperative parameters such as neoadjuvant chemotherapy, radiotherapy, and immunotherapy were not included, making it impossible for us to perform a comprehensive analyses of these potential parameters. Secondly, the data used in the present study were downloaded from an open-accessed database, making our study retrospective in nature.…”

Long intergenic noncoding RNA smad7 (Linc‐smad7) promotes the epithelial‐mesenchymal transition of HCC by targeting the miR‑125b/SIRT6 axis

“…A group of studies reveal that lncRNAs are able to function as ceRNAs through their miRNA response elements to interfere with miRNAs and their target mRNAs. [29][30][31] Therefore, lncRNA-miRNA-mRNA interactional networks have been confirmed to be an important mechanism underlying the carcinogenesis and development of different types of cancer, [32][33][34] including HCC. 35 In the current study, miR-125b was identified as a targeting miRNA that possesses binding sites for Linc-smad7.…”