Abstract
BackgroundRecent evidence has indicated that long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) to modulate mRNAs expression by sponging microRNAs (miRNAs). However, the specific mechanism and function of lncRNA-miRNA-mRNA regulatory network in non-small cell lung cancer (NSCLC) remains unclear.Materials and MethodsWe constructed a lung cancer related lncRNA-mRNA network (LCLMN) by integrating differentially expressed genes (DEGs) with miRNA-target interactions. We further performed topological feature analysis and random walk with restart (RWR) analysis of LCLMN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the target DEGs in LCLMN. The expression levels of significant lncRNAs in NSCLC were validated by quantitative real-time PCR (RT-qPCR). The prognostic value of the potential lncRNA was evaluated by Kaplan-Meier analysis.ResultsA total of 33 lncRNA nodes, 580 mRNA nodes and 2105 edges were identified from LCLMN. Based on functional enrichment analysis and co-expression analysis, lncRNA EPB41L4A-AS1 was demonstrated to be correlated with the tumorigenesis of NSCLC. RT-qPCR results confirmed that the expression levels of lncRNA EPB41L4A-AS1 in NSCLC tissues were downregulated compared with adjacent non-cancerous tissues. Kaplan-Meier analysis showed that high expression of lncRNA EPB41L4A-AS1 was associated with better overall survival (OS) in NSCLC patients. Further investigation identified that high expression levels of COL4A3BP, CDS2, PURA, PDCD6IP, and TMEM245 were also correlated with better OS in NSCLC patients.ConclusionIn this study, we constructed a lncRNA-miRNA-mRNA ceRNA network to investigate potential prognostic biomarkers for NSCLC. We found that lncRNA EPB41L4A-AS1 could function as a regulator in the pathogenesis of NSCLC.
Highlights
Lung cancer is the most common cancer for both men and women (11.6% of total cases) and the leading cause of cancerrelated death (18.4% of total cancer deaths) in the world (Bray et al, 2018)
We identified 1072 differentially expressed mRNAs and 199 differentially expressed long non-coding RNAs (lncRNAs), which were considered as potential regulators in the occurrence and development of lung cancer
In the overlapping part of these nodes, we found a total of three lncRNAs (EPB41L4AAS1, KB-1732A1.1, RP11-390P2.4), which might function as crucial regulators in the biological process of lung cancer (Table 2 and Figure 3D)
Summary
Lung cancer is the most common cancer for both men and women (11.6% of total cases) and the leading cause of cancerrelated death (18.4% of total cancer deaths) in the world (Bray et al, 2018). As a kind of subclass of ncRNAs, long non-coding RNAs (lncRNAs) are functionally defined as transcripts longer than 200 nt and have key roles in gene regulation (Beermann et al, 2016; Schmitt and Chang, 2016). Increasing evidence had revealed that abnormal expression of lncRNAs were involved cancer development and may serve as prognostic biomarkers and therapeutic targets in cancer (Huarte, 2015; Chi et al, 2018; Kopp and Mendell, 2018). Recent evidence has indicated that long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) to modulate mRNAs expression by sponging microRNAs (miRNAs). The specific mechanism and function of lncRNA-miRNA-mRNA regulatory network in non-small cell lung cancer (NSCLC) remains unclear
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