Abstract
BackgroundNon-small cell lung cancer (NSCLC) is a major subtype of lung cancer with high malignancy and bad prognosis, consisted of lung adenocarcinomas (LUAD) and lung squamous cell carcinomas (LUSC) chiefly. Multiple studies have indicated that competing endogenous RNA (ceRNA) network centered long noncoding RNAs (lncRNAs) can regulate gene expression and the progression of various cancers. However, the research about lncRNAs-mediated ceRNA network in LUAD is still lacking.MethodsIn this study, we analyzed the RNA-seq database from The Cancer Genome Atlas (TCGA) and obtained dysregulated lncRNAs in NSCLC, then further identified survival associated lncRNAs through Kaplan–Meier analysis. Quantitative real time PCR (qRT-PCR) was performed to confirm their expression in LUAD tissues and cell lines. The ceRNA networks were constructed based on DIANA-TarBase and TargetScan databases and visualized with OmicShare tools. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to investigate the potential function of ceRNA networks.ResultsIn total, 1,437 and 1,699 lncRNAs were found to be up-regulated in LUAD and LUSC respectively with 895 lncRNAs overlapping (|log2FC| > 3, adjusted P value <0.01). Among which, 222 lncRNAs and 46 lncRNAs were associated with the overall survival (OS) of LUAD and LUSC, and 18 out of 222 up-regulated lncRNAs were found to have inverse correlation with LUAD patients’ OS (|log2FC| > 3, adjusted P value < 0.02). We selected 3 lncRNAs (CASC8, LINC01842 and VPS9D1-AS1) out of these 18 lncRNAs and confirmed their overexpression in lung cancer tissues and cells. CeRNA networks were further constructed centered CASC8, LINC01842 and VPS9D1-AS1 with 3 miRNAs and 100 mRNAs included respectively.ConclusionThrough comprehensively analyses of TCGA, our study identified specific lncRNAs as candidate diagnostic and prognostic biomarkers for LUAD. The novel ceRNA network we created provided more insights into the regulatory mechanisms underlying LUAD.
Highlights
Lung cancer is one of the most frequently diagnosed cancers and leading causes of cancer-related mortality worldwide with nearly 1.8 million new cases every year (Ferlay et al, 2015)
This study aimed to investigate specific long noncoding RNAs (lncRNAs) and related competing endogenous RNA (ceRNA) networks that may be involved in the molecular mechanisms of lung adenocarcinomas (LUAD) and provide potential diagnostic biomarkers for LUAD
Identification of lung cancer specific lncRNAs In this study, we investigated the RNA expression levels in 535 LUAD samples compared with 59 adjacent non-tumorous tissues and 502 lung squamous cell carcinomas (LUSC) samples compared with 49 normal tissues, and the RNA-sequencing data were all obtained from The Cancer Genome Atlas (TCGA) database
Summary
Lung cancer is one of the most frequently diagnosed cancers and leading causes of cancer-related mortality worldwide with nearly 1.8 million new cases every year (Ferlay et al, 2015). Lung adenocarcinoma (LUAD) is the most common pathologic subtype of NSCLC, which comprises nearly 40% of lung cancer cases (Xiong et al, 2018). Multiple studies have indicated that competing endogenous RNA (ceRNA) network centered long noncoding RNAs (lncRNAs) can regulate gene expression and the progression of various cancers. Methods: In this study, we analyzed the RNA-seq database from The Cancer Genome Atlas (TCGA) and obtained dysregulated lncRNAs in NSCLC, further identified survival associated lncRNAs through Kaplan–Meier analysis. We selected 3 lncRNAs (CASC8, LINC01842 and VPS9D1-AS1) out of these 18 lncRNAs and confirmed their overexpression in lung cancer tissues and cells. CeRNA networks were further constructed centered CASC8, LINC01842 and VPS9D1-AS1 with 3 miRNAs and 100 mRNAs included respectively. Conclusion: Through comprehensively analyses of TCGA, our study identified specific lncRNAs as candidate diagnostic and prognostic biomarkers for LUAD
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