Xiao-Jun Wang1,2, Jing Gao2,3,4, Zhuo Wang1,5, Qin Yu1,6. 1. The First School of Clinical Medicine, Lanzhou University, Lanzhou, China. 2. Department of Respiratory Medicine, Gansu Provincial Hospital, Lanzhou, China. 3. Respiratory Medicine Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden. 4. Department of Pulmonary Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. 5. Department of Pathology Medicine, Gansu Provincial Hospital, Lanzhou, China. 6. Department of Respiratory Medicine, The First Hospital of Lanzhou University, Lanzhou, China.
Abstract
BACKGROUND: Lung 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. METHODS: Differentially 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). RESULTS: The 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. CONCLUSION: This 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.
BACKGROUND: Lung 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. METHODS: Differentially 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). RESULTS: The 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. CONCLUSION: This 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.
Authors: Riccardo Cazzoli; Fiamma Buttitta; Marta Di Nicola; Sara Malatesta; Antonio Marchetti; William N Rom; Harvey I Pass Journal: J Thorac Oncol Date: 2013-09 Impact factor: 15.609
Authors: Claudia I Henschke; David F Yankelevitz; Daniel M Libby; Mark W Pasmantier; James P Smith; Olli S Miettinen Journal: N Engl J Med Date: 2006-10-26 Impact factor: 91.245
Authors: Margarita González-Vallinas; Manuel Rodríguez-Paredes; Marco Albrecht; Carsten Sticht; Damian Stichel; Julian Gutekunst; Adriana Pitea; Steffen Sass; Francisco J Sánchez-Rivera; Justo Lorenzo-Bermejo; Jennifer Schmitt; Carolina De La Torre; Arne Warth; Fabian J Theis; Nikola S Müller; Norbert Gretz; Thomas Muley; Michael Meister; Darjus F Tschaharganeh; Peter Schirmacher; Franziska Matthäus; Kai Breuhahn Journal: Mol Cancer Res Date: 2018-01-12 Impact factor: 5.852
Authors: Silvia Licciulli; Jacqueline L Avila; Linda Hanlon; Scott Troutman; Matteo Cesaroni; Smitha Kota; Brian Keith; M Celeste Simon; Ellen Puré; Fred Radtke; Anthony J Capobianco; Joseph L Kissil Journal: Cancer Res Date: 2013-08-13 Impact factor: 12.701
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702