Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis
BackgroundLung adenocarcinoma (LUAD) is a common lung cancer with a high mortality, for which microRNAs (miRNAs) play a vital role in its regulation. Multiple messenger RNAs (mRNAs) may be regulated by miRNAs, involved in LUAD tumorigenesis and progression. However, the miRNA–mRNA regulatory network...
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doaj-210bfa17c81f44e09d82fe77f17e60442021-02-18T08:12:26ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01910.3389/fcell.2021.641840641840Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics AnalysisXiao-Jun Wang0Xiao-Jun Wang1Jing Gao2Jing Gao3Jing Gao4Zhuo Wang5Zhuo Wang6Qin Yu7Qin Yu8The First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Respiratory Medicine, Gansu Provincial Hospital, Lanzhou, ChinaDepartment of Respiratory Medicine, Gansu Provincial Hospital, Lanzhou, ChinaRespiratory Medicine Unit, Department of Medicine, Karolinska Institute, Stockholm, SwedenDepartment of Pulmonary Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, FinlandThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Pathology Medicine, Gansu Provincial Hospital, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Respiratory Medicine, The First Hospital of Lanzhou University, Lanzhou, ChinaBackgroundLung adenocarcinoma (LUAD) is a common lung cancer with a high mortality, for which microRNAs (miRNAs) play a vital role in its regulation. Multiple messenger RNAs (mRNAs) may be regulated by miRNAs, involved in LUAD tumorigenesis and progression. However, the miRNA–mRNA regulatory network involved in LUAD has not been fully elucidated.MethodsDifferentially expressed miRNAs and mRNA were derived from the Cancer Genome Atlas (TCGA) dataset in tissue samples and from our microarray data in plasma (GSE151963). Then, common differentially expressed (Co-DE) miRNAs were obtained through intersected analyses between the above two datasets. An overlap was applied to confirm the Co-DEmRNAs identified both in targeted mRNAs and DEmRNAs in TCGA. A miRNA–mRNA regulatory network was constructed using Cytoscape. The top five miRNA were identified as hub miRNA by degrees in the network. The functions and signaling pathways associated with the hub miRNA-targeted genes were revealed through Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The key mRNAs in the protein–protein interaction (PPI) network were identified using the STRING database and CytoHubba. Survival analyses were performed using Gene Expression Profiling Interactive Analysis (GEPIA).ResultsThe miRNA–mRNA regulatory network consists of 19 Co-DEmiRNAs and 760 Co-DEmRNAs. The five miRNAs (miR-539-5p, miR-656-3p, miR-2110, let-7b-5p, and miR-92b-3p) in the network were identified as hub miRNAs by degrees (>100). The 677 Co-DEmRNAs were targeted mRNAs from the five hub miRNAs, showing the roles in the functional analyses of the GO analysis and KEGG pathways (inclusion criteria: 836 and 48, respectively). The PPI network and Cytoscape analyses revealed that the top ten key mRNAs were NOTCH1, MMP2, IGF1, KDR, SPP1, FLT1, HGF, TEK, ANGPT1, and PDGFB. SPP1 and HGF emerged as hub genes through survival analysis. A high SPP1 expression indicated a poor survival, whereas HGF positively associated with survival outcomes in LUAD.ConclusionThis study investigated a miRNA–mRNA regulatory network associated with LUAD, exploring the hub miRNAs and potential functions of mRNA in the network. These findings contribute to identify new prognostic markers and therapeutic targets for LUAD patients in clinical settings.https://www.frontiersin.org/articles/10.3389/fcell.2021.641840/fulllung adenocarcinomamicroRNAshub genesbioinformaticsprognostic marker |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiao-Jun Wang Xiao-Jun Wang Jing Gao Jing Gao Jing Gao Zhuo Wang Zhuo Wang Qin Yu Qin Yu |
spellingShingle |
Xiao-Jun Wang Xiao-Jun Wang Jing Gao Jing Gao Jing Gao Zhuo Wang Zhuo Wang Qin Yu Qin Yu Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis Frontiers in Cell and Developmental Biology lung adenocarcinoma microRNAs hub genes bioinformatics prognostic marker |
author_facet |
Xiao-Jun Wang Xiao-Jun Wang Jing Gao Jing Gao Jing Gao Zhuo Wang Zhuo Wang Qin Yu Qin Yu |
author_sort |
Xiao-Jun Wang |
title |
Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis |
title_short |
Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis |
title_full |
Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis |
title_fullStr |
Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis |
title_full_unstemmed |
Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis |
title_sort |
identification of a potentially functional microrna–mrna regulatory network in lung adenocarcinoma using a bioinformatics analysis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-02-01 |
description |
BackgroundLung adenocarcinoma (LUAD) is a common lung cancer with a high mortality, for which microRNAs (miRNAs) play a vital role in its regulation. Multiple messenger RNAs (mRNAs) may be regulated by miRNAs, involved in LUAD tumorigenesis and progression. However, the miRNA–mRNA regulatory network involved in LUAD has not been fully elucidated.MethodsDifferentially expressed miRNAs and mRNA were derived from the Cancer Genome Atlas (TCGA) dataset in tissue samples and from our microarray data in plasma (GSE151963). Then, common differentially expressed (Co-DE) miRNAs were obtained through intersected analyses between the above two datasets. An overlap was applied to confirm the Co-DEmRNAs identified both in targeted mRNAs and DEmRNAs in TCGA. A miRNA–mRNA regulatory network was constructed using Cytoscape. The top five miRNA were identified as hub miRNA by degrees in the network. The functions and signaling pathways associated with the hub miRNA-targeted genes were revealed through Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The key mRNAs in the protein–protein interaction (PPI) network were identified using the STRING database and CytoHubba. Survival analyses were performed using Gene Expression Profiling Interactive Analysis (GEPIA).ResultsThe miRNA–mRNA regulatory network consists of 19 Co-DEmiRNAs and 760 Co-DEmRNAs. The five miRNAs (miR-539-5p, miR-656-3p, miR-2110, let-7b-5p, and miR-92b-3p) in the network were identified as hub miRNAs by degrees (>100). The 677 Co-DEmRNAs were targeted mRNAs from the five hub miRNAs, showing the roles in the functional analyses of the GO analysis and KEGG pathways (inclusion criteria: 836 and 48, respectively). The PPI network and Cytoscape analyses revealed that the top ten key mRNAs were NOTCH1, MMP2, IGF1, KDR, SPP1, FLT1, HGF, TEK, ANGPT1, and PDGFB. SPP1 and HGF emerged as hub genes through survival analysis. A high SPP1 expression indicated a poor survival, whereas HGF positively associated with survival outcomes in LUAD.ConclusionThis study investigated a miRNA–mRNA regulatory network associated with LUAD, exploring the hub miRNAs and potential functions of mRNA in the network. These findings contribute to identify new prognostic markers and therapeutic targets for LUAD patients in clinical settings. |
topic |
lung adenocarcinoma microRNAs hub genes bioinformatics prognostic marker |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.641840/full |
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