Dataset Information

Competing endogenous RNA (ceRNA) hypothetic model based on comprehensive analysis of long non-coding RNA expression in lung adenocarcinoma.

ABSTRACT: Background:Non-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. Methods:In 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. Results:In 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. Conclusion:Through 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.

SUBMITTER: Wang X

PROVIDER: S-EPMC6842565 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Competing endogenous RNA (ceRNA) hypothetic model based on comprehensive analysis of long non-coding RNA expression in lung adenocarcinoma.

Wang Xiwen X Su Rui R Guo Qiqiang Q Liu Jia J Ruan Banlai B Wang Guiling G

PeerJ 20191107

<h4>Background</h4>Non-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.<h4>Methods ...[more]

PMID: 31720124

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Project description:Gastric cancer (GC) is a common type of cancer, and identification of novel diagnostic biomarkers associated with this disease is important. The present study aimed to identify novel diagnostic biomarkers associated with the prognosis of GC, using an integrated bioinformatics approach. Differentially expressed long non-coding RNAs (lncRNAs) associated with GC were identified using Gene Expression Omnibus datasets (GSE58828, GSE72305 and GSE99416) and The Cancer Genome Atlas database. A competing endogenous RNA network that incorporated five lncRNAs [long intergenic non-protein coding RNA 501 (LINC00501), LINC00365, SOX21 antisense divergent transcript 1 (SOX21-AS1), GK intronic transcript 1 (GK-IT1) and DLEU7 antisense RNA 1 (DLEU7-AS1)], 29 microRNAs and 114 mRNAs was constructed. Gene Ontology and protein-protein interaction network analyses revealed that these lncRNAs may be involved in 'biological regulation', 'metabolic process', 'cell communication', 'developmental process', 'cell proliferation', 'reproduction' and the 'cell cycle'. The results of receiver operating characteristic curve analysis demonstrated that LINC00501 (AUC=0.819), LINC00365 (AUC=0.580), SOX21-AS1 (AUC=0.736), GK-IT1 (AUC=0.823) and DLEU7-AS1 (AUC=0.932) had the potential to become valuable diagnostic biomarkers for GC. Associations with clinicopathological characteristics demonstrated that LINC00501 expression was significantly associated with sex (P=0.015) and tumor grade (P=0.022). Furthermore, LINC00365 expression was significantly associated with lymph node metastasis (P=0.025). Gene set enrichment analysis revealed that LINC00501, LINC00365 and SOX21-AS1 were enriched in signaling pathways associated with GC. Reverse transcription-quantitative PCR analysis demonstrated that LINC00501 expression (P=0.043) was significantly upregulated in GC tissues, whereas the expression levels of LINC00365 (P=0.033) and SOX21-AS1 (P=0.037) were significantly downregulated in GC tissues. Taken together, the results of the present study suggest that LINC00501, LINC00365, SOX21-AS1, GK-IT1 and DLEU7-AS1 may be used as novel diagnostic biomarkers for GC, and may be functionally associated with GC development and progression.

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Dataset Information

Competing endogenous RNA (ceRNA) hypothetic model based on comprehensive analysis of long non-coding RNA expression in lung adenocarcinoma.

Publications

Competing endogenous RNA (ceRNA) hypothetic model based on comprehensive analysis of long non-coding RNA expression in lung adenocarcinoma.

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