Comprehensive Analysis of Aberrantly Expressed Profiles of lncRNAs and miRNAs with Associated ceRNA Network in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.Pathol Oncol Res. 2020 Jul; 26(3):1935-1945.PO
Lung cancer (LC) continues to be the leading cause of cancer-related deaths worldwide and the prognosis remains poor worldwide. At present, the long non-coding RNAs (lncRNAs) was considered as a part of competing endogenous RNA (ceRNA) network act as natural microRNA (miRNA) sponges to regulate protein-coding gene expression. However, functional roles of lncRNA-mediated ceRNAs in LC are insufficiently understood. To classify the specific mechanism of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), we comprehensively compared the expression profiles of mRNAs, lncRNAs and miRNAs obtained from 509 LUAD, 473 LUSC tissues and 49 adjacent non-cancerous lung tissues, based on The Cancer Genome Atlas (TCGA). After screening for differently expressed (DE) mRNAs, DEmiRNAs, DElncRNAs and weighted gene co-expression network analysis (WGCNA) (|log2FC| > 2.0 and an adjusted p value <0.05), a total of 4478 DEmRNAs, 526 DElncRNAs and 75 DEmiRNAs in LUAD, while 6237 DEmRNAs, 843 DElncRNAs and 117 DEmiRNAs in LUSC were discovered. Interaction (PPI) network analysis was performed to identify 656 nodes and 2987 edges (minimum required interaction score > 0.9), as well as 8 different protein-protein interactions. Gene ontology (GO) analysis mainly associated with cell proliferation. KEGG pathway enrichment analyses most partly associated with metabolism pathway and cytokine-cytokine receptor interaction. Finally, the dysregulated lncRNA-miRNA-ceRNA network was constructed based on correlation analyses and a total of 62 dysregulated lncRNAs, 28 DEmRNAs and 18 DEmiRNAs were involved. The most significant lncRNAs included DElncRNAs, LINC00641 and AC004947.2, miRNAs included miR-6860, miR-1285-3p, miR-767-3p and miR-7974, mRNAs included MAP3K3, FGD3 and ATP1B2. Then we analyzed and described the potential characteristics of biological function and pathological roles of the LUAD and LUSC ceRNA co-regulatory network. Our findings revealed ceRNA network will be beneficial for promoting the understanding of lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of LUAD and LUSC.