Construction and Analysis of Survival-Associated Competing Endogenous RNA Network in Lung Adenocarcinoma
Open Access
- 12 February 2021
- journal article
- research article
- Published by Hindawi Limited in BioMed Research International
- Vol. 2021, 1-17
- https://doi.org/10.1155/2021/4093426
Abstract
Increasing evidence has shown that noncoding RNAs play significant roles in the initiation, progression, and metastasis of tumours via participating in competing endogenous RNA (ceRNA) networks. However, the survival-associated ceRNA in lung adenocarcinoma (LUAD) remains poorly understood. In this study, we aimed to investigate the regulatory mechanisms underlying ceRNA in LUAD to identify novel prognostic factors. mRNA, lncRNA, and miRNA sequencing data obtained from the GDC data portal were utilized to identify differentially expressed (DE) RNAs. Survival-related RNAs were recognized using univariate Kaplan-Meier survival analysis. We performed functional enrichment analysis of survival-related mRNAs using the clusterProfiler package of R and STRING. lncRNA-miRNA and miRNA-mRNA interactions were predicted based on miRcode, Starbase, and miRanda. Subsequently, the survival-associated ceRNA network was constructed for LUAD. Multivariate Cox regression analysis was used to identify prognostic factors. Finally, we acquired 15 DE miRNAs, 49 DE lncRNAs, and 843 DE mRNAs associated with significant overall survival. Functional enrichment analysis indicated that survival-related DE mRNAs were enriched in cell cycle. The survival-associated lncRNA-miRNA-mRNA ceRNA network was constructed using five miRNAs, 49 mRNAs, and 21 lncRNAs. Furthermore, seven hub RNAs (LINC01936, miR-20a-5p, miR-31-5p, TNS1, TGFBR2, SMAD7, and NEDD4L) were identified based on the ceRNA network. LINC01936 and miR-31-5p were found to be significant using the multifactorial Cox regression model. In conclusion, we successfully constructed a survival-related lncRNA-miRNA-mRNA ceRNA regulatory network in LUAD and identified seven hub RNAs, which provide novel insights into the regulatory molecular mechanisms associated with survival of LUAD, and identified two independent prognostic predictors for LUAD.Funding Information
- Guangdong Pharmaceutical University (2020KZDZX1126)
This publication has 69 references indexed in Scilit:
- miRcode: a map of putative microRNA target sites in the long non-coding transcriptomeBioinformatics, 2012
- clusterProfiler: an R Package for Comparing Biological Themes Among Gene ClustersOMICS: A Journal of Integrative Biology, 2012
- A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?Cell, 2011
- Osteoblast mineralization requires β1 integrin/ICAP-1–dependent fibronectin depositionThe Journal of cell biology, 2011
- Ubiquitin Ligase Nedd4L Targets Activated Smad2/3 to Limit TGF-β SignalingMolecular Cell, 2009
- Human T-cell leukemia virus type I infects human lung epithelial cells and induces gene expression of cytokines, chemokines and cell adhesion moleculesRetrovirology, 2008
- The microRNA.org resource: targets and expressionNucleic Acids Research, 2007
- Erlotinib in Lung Cancer — Molecular and Clinical Predictors of OutcomeThe New England Journal of Medicine, 2005
- Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction NetworksGenome Research, 2003
- Signal transduction and the Ets family of transcription factorsOncogene, 2000