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Integrated Analysis of lncRNA-miRNA-mRNA ceRNA Network and Identification of Hub lncRNAs in Molecular Subtypes of
Seyed Navid Goftari1, Ahmad Reza Bahrami1,2, Maryam M Matin1,2
1Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Background:
Gastric cancer (GC) is the fourth most common cause of death among cancers in the world, and the most prevalent type of GC is adenocarcinoma. The Cancer Genome Atlas (TCGA) project introduced 4 molecular subtypes of GC adenocarcinomas: Epstein-Barr virus (EBV), microsatellite instability (MSI), genomically stable (GS), and chromosomal instability (CIN). However, the function of long noncoding RNAs (lncRNAs) in these subtypes still remains unknown. Here, we aimed to construct a competing endogenous RNA (ceRNA) network to clarify the role of lncRNAs in each GC subtype and predict patients' overall relapse-free survival (RFS) time.
Methods:
The RNA-seq data of miRNAs, lncRNAs, and mRNAs related to different GC subtypes and their corresponding normal samples from TCGA were analyzed, and a combination of signed and unsigned weighted gene co-expression network analysis (WGCNA) (csuWGCNA) was recruited to determine co-expressing gene modules. Then, lncRNA-miRNA and miRNA-mRNA interactions were predicted, and the ceRNA regulatory network was established, followed by the identification of hub lncRNAs for any GC subtype. Gene set enrichment analyses were applied to protein-coding genes of each module to investigate their functions. Finally, survival analysis was performed for identified hub lncRNAs.
Results:
Differentially expressed lncRNAs, miRNAs, and mRNAs related to each GC subtype were identified, ceRNA networks were constructed, and in each subtype, the top 5 lncRNAs with the most MCC scores were chosen as hub lncRNAs. Survival analysis revealed that AC138356.1, LINC01270, and AL118506.1 lncRNAs were associated with the RFS of CIN subtype, LINC02099, AL157871.2, AC068580.3, and AC004264.1 lncRNAs with EBV subtype, AL117335.1 and AC011416.3 lncRNAs with MSI subtype, and MIR210HG and LINC00565 lncRNAs with GS subtype patients.
Conclusion:
The identified hub lncRNAs provide insights for understanding molecular mechanisms underlying GC subtype transformation and may be useful to predict the RFS of corresponding patients; more research is required to confirm the results.
