Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer

Jingyi Chen,Yulan Liu,Di Wang,Jingzhu Guo,Tingru Lin,Weidong Yu,Mei Li,Jie Sun,Yuxuan Song,Yu Zhang

doi:10.1186/s12885-021-07995-2

Abstract

BackgroundCompeting endogenous RNA (ceRNA) represents a class of RNAs (e.g., long noncoding RNAs [lncRNAs]) with microRNA (miRNA) binding sites, which can competitively bind miRNA and inhibit its regulation of target genes. Increasing evidence has underscored the involvement of dysregulated ceRNA networks in the occurrence and progression of colorectal cancer (CRC). The purpose of this study was to construct a ceRNA network related to the prognosis of CRC and further explore the potential mechanisms that affect this prognosis.MethodsRNA-Seq and miRNA-Seq data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed lncRNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs), and a prognosis-related ceRNA network was constructed based on DElncRNA survival analysis. Subsequently, pathway enrichment, Pearson correlation, and Gene Set Enrichment Analysis (GSEA) were performed to determine the function of the genes in the ceRNA network. Gene Expression Profiling Interactive Analysis (GEPIA) and immunohistochemistry (IHC) were also used to validate differential gene expression. Finally, the correlation between lncRNA and immune cell infiltration in the tumor microenvironment was evaluated based on the CIBERSORT algorithm.ResultsA prognostic ceRNA network was constructed with eleven key survival-related DElncRNAs (MIR4435-2HG, NKILA, AFAP1-AS1, ELFN1-AS1, AC005520.2, AC245884.8, AL354836.1, AL355987.4, AL591845.1, LINC02038, and AC104823.1), 54 DEmiRNAs, and 308 DEmRNAs. The MIR4435-2HG- and ELFN1-AS1-associated ceRNA subnetworks affected and regulated the expression of the COL5A2, LOX, OSBPL3, PLAU, VCAN, SRM, and E2F1 target genes and were found to be related to prognosis and tumor-infiltrating immune cell types.ConclusionsMIR4435-2HG and ELFN1-AS1 are associated with prognosis and tumor-infiltrating immune cell types and could represent potential prognostic biomarkers or therapeutic targets in colorectal carcinoma.

Highlights

Competing endogenous RNA represents a class of RNAs with microRNA binding sites, which can competitively bind miRNA and inhibit its regulation of target genes
Based on the prognosis-related Competing endogenous RNA (ceRNA) network, we evaluated the associations between key Long noncoding RNA (lncRNA) and the clinical features of Colorectal cancer (CRC) patients using the R package “ggpubr”
Prediction of lncRNA–miRNA and miRNA–Message RNA (mRNA) interactions We predicted lncRNA–miRNA interaction pairs based on DElncRNAs using the online tool DIANA-LncBase version 3 and found that 153 of the 217 DElncRNAs might target 199 of the 376 DEmiRNAs

Summary

Introduction

Competing endogenous RNA (ceRNA) represents a class of RNAs (e.g., long noncoding RNAs [lncRNAs]) with microRNA (miRNA) binding sites, which can competitively bind miRNA and inhibit its regulation of target genes. Increasing evidence has underscored the involvement of dysregulated ceRNA networks in the occurrence and progression of colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) are noncoding transcripts that range from 200 to 100,000 nucleotides in length and lack protein-coding capacity. They function as signals, decoys, guides, and scaffolds in gene regulatory networks [3]. An increasing number of lncRNAs have been found to participate in CRC initiation and progression by functioning as competing endogenous RNAs (ceRNAs) [4,5,6]. Recent studies showed that ceRNA crosstalk was involved in various biological processes, including CRC cell proliferation, invasion, epithelial-to-mesenchymal transition (EMT), metastasis, and immune infiltration [9,10,11,12,13]

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