Co-Expression Network Analysis Unveiled lncRNA-mRNA Links Correlated to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance and/or Intermediate Epithelial-to-Mesenchymal Transition Phenotypes in a Human Non-Small Cell Lung Cancer Cellular Model System
We investigated mRNA-lncRNA co-expression patterns in a cellular model system of non-small cell lung cancer (NSCLC) sensitive and resistant to the epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib/gefitinib. The aim of this study was to unveil insights into the com...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/25/7/3863 |
| _version_ | 1797212514777300992 |
|---|---|
| author | Valentina Fustaino Giuliana Papoff Francesca Ruberti Giovina Ruberti |
| author_facet | Valentina Fustaino Giuliana Papoff Francesca Ruberti Giovina Ruberti |
| author_sort | Valentina Fustaino |
| collection | DOAJ |
| description | We investigated mRNA-lncRNA co-expression patterns in a cellular model system of non-small cell lung cancer (NSCLC) sensitive and resistant to the epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib/gefitinib. The aim of this study was to unveil insights into the complex mechanisms of NSCLC targeted therapy resistance and epithelial-to-mesenchymal transition (EMT). Genome-wide RNA expression was quantified for weighted gene co-expression network analysis (WGCNA) to correlate the expression levels of mRNAs and lncRNAs. Functional enrichment analysis and identification of lncRNAs were conducted on modules associated with the EGFR-TKI response and/or intermediate EMT phenotypes. We constructed lncRNA-mRNA co-expression networks and identified key modules and their enriched biological functions. Processes enriched in the selected modules included RHO (A, B, C) GTPase and regulatory signaling pathways, apoptosis, inflammatory and interleukin signaling pathways, cell adhesion, cell migration, cell and extracellular matrix organization, metabolism, and lipid metabolism. Interestingly, several lncRNAs, already shown to be dysregulated in cancer, are connected to a small number of mRNAs, and several lncRNAs are interlinked with each other in the co-expression network. |
| first_indexed | 2024-04-24T10:43:36Z |
| format | Article |
| id | doaj.art-a725140184ac4fcb9f53f3c5d531ca89 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:43:36Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a725140184ac4fcb9f53f3c5d531ca892024-04-12T13:19:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01257386310.3390/ijms25073863Co-Expression Network Analysis Unveiled lncRNA-mRNA Links Correlated to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance and/or Intermediate Epithelial-to-Mesenchymal Transition Phenotypes in a Human Non-Small Cell Lung Cancer Cellular Model SystemValentina Fustaino0Giuliana Papoff1Francesca Ruberti2Giovina Ruberti3Institute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Campus Adriano Buzzati Traverso, Via E. Ramarini 32, 00015 Monterotondo (Roma), ItalyInstitute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Campus Adriano Buzzati Traverso, Via E. Ramarini 32, 00015 Monterotondo (Roma), ItalyInstitute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Campus Adriano Buzzati Traverso, Via E. Ramarini 32, 00015 Monterotondo (Roma), ItalyInstitute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Campus Adriano Buzzati Traverso, Via E. Ramarini 32, 00015 Monterotondo (Roma), ItalyWe investigated mRNA-lncRNA co-expression patterns in a cellular model system of non-small cell lung cancer (NSCLC) sensitive and resistant to the epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib/gefitinib. The aim of this study was to unveil insights into the complex mechanisms of NSCLC targeted therapy resistance and epithelial-to-mesenchymal transition (EMT). Genome-wide RNA expression was quantified for weighted gene co-expression network analysis (WGCNA) to correlate the expression levels of mRNAs and lncRNAs. Functional enrichment analysis and identification of lncRNAs were conducted on modules associated with the EGFR-TKI response and/or intermediate EMT phenotypes. We constructed lncRNA-mRNA co-expression networks and identified key modules and their enriched biological functions. Processes enriched in the selected modules included RHO (A, B, C) GTPase and regulatory signaling pathways, apoptosis, inflammatory and interleukin signaling pathways, cell adhesion, cell migration, cell and extracellular matrix organization, metabolism, and lipid metabolism. Interestingly, several lncRNAs, already shown to be dysregulated in cancer, are connected to a small number of mRNAs, and several lncRNAs are interlinked with each other in the co-expression network.https://www.mdpi.com/1422-0067/25/7/3863NSCLCWGCNAlncRNA-mRNA networksEGFR-TKI resistanceintermediate EMT phenotypes |
| spellingShingle | Valentina Fustaino Giuliana Papoff Francesca Ruberti Giovina Ruberti Co-Expression Network Analysis Unveiled lncRNA-mRNA Links Correlated to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance and/or Intermediate Epithelial-to-Mesenchymal Transition Phenotypes in a Human Non-Small Cell Lung Cancer Cellular Model System International Journal of Molecular Sciences NSCLC WGCNA lncRNA-mRNA networks EGFR-TKI resistance intermediate EMT phenotypes |
| title | Co-Expression Network Analysis Unveiled lncRNA-mRNA Links Correlated to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance and/or Intermediate Epithelial-to-Mesenchymal Transition Phenotypes in a Human Non-Small Cell Lung Cancer Cellular Model System |
| title_full | Co-Expression Network Analysis Unveiled lncRNA-mRNA Links Correlated to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance and/or Intermediate Epithelial-to-Mesenchymal Transition Phenotypes in a Human Non-Small Cell Lung Cancer Cellular Model System |
| title_fullStr | Co-Expression Network Analysis Unveiled lncRNA-mRNA Links Correlated to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance and/or Intermediate Epithelial-to-Mesenchymal Transition Phenotypes in a Human Non-Small Cell Lung Cancer Cellular Model System |
| title_full_unstemmed | Co-Expression Network Analysis Unveiled lncRNA-mRNA Links Correlated to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance and/or Intermediate Epithelial-to-Mesenchymal Transition Phenotypes in a Human Non-Small Cell Lung Cancer Cellular Model System |
| title_short | Co-Expression Network Analysis Unveiled lncRNA-mRNA Links Correlated to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance and/or Intermediate Epithelial-to-Mesenchymal Transition Phenotypes in a Human Non-Small Cell Lung Cancer Cellular Model System |
| title_sort | co expression network analysis unveiled lncrna mrna links correlated to epidermal growth factor receptor tyrosine kinase inhibitor resistance and or intermediate epithelial to mesenchymal transition phenotypes in a human non small cell lung cancer cellular model system |
| topic | NSCLC WGCNA lncRNA-mRNA networks EGFR-TKI resistance intermediate EMT phenotypes |
| url | https://www.mdpi.com/1422-0067/25/7/3863 |
| work_keys_str_mv | AT valentinafustaino coexpressionnetworkanalysisunveiledlncrnamrnalinkscorrelatedtoepidermalgrowthfactorreceptortyrosinekinaseinhibitorresistanceandorintermediateepithelialtomesenchymaltransitionphenotypesinahumannonsmallcelllungcancercellularmodelsystem AT giulianapapoff coexpressionnetworkanalysisunveiledlncrnamrnalinkscorrelatedtoepidermalgrowthfactorreceptortyrosinekinaseinhibitorresistanceandorintermediateepithelialtomesenchymaltransitionphenotypesinahumannonsmallcelllungcancercellularmodelsystem AT francescaruberti coexpressionnetworkanalysisunveiledlncrnamrnalinkscorrelatedtoepidermalgrowthfactorreceptortyrosinekinaseinhibitorresistanceandorintermediateepithelialtomesenchymaltransitionphenotypesinahumannonsmallcelllungcancercellularmodelsystem AT giovinaruberti coexpressionnetworkanalysisunveiledlncrnamrnalinkscorrelatedtoepidermalgrowthfactorreceptortyrosinekinaseinhibitorresistanceandorintermediateepithelialtomesenchymaltransitionphenotypesinahumannonsmallcelllungcancercellularmodelsystem |