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Comparative mRNA and miRNA transcriptome analysis of a mouse model of IGFIR-driven lung cancer

Mouse models of cancer play an important role in elucidating the molecular mechanisms that contribute to tumorigenesis. The extent to which these models resemble one another and their human counterparts at the molecular level is critical in understanding tumorigenesis. In this study, we carried out...

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Autores principales: Jones, Robert A., Franks, Sarah E., Moorehead, Roger A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226179/
https://www.ncbi.nlm.nih.gov/pubmed/30412601
http://dx.doi.org/10.1371/journal.pone.0206948
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author Jones, Robert A.
Franks, Sarah E.
Moorehead, Roger A.
author_facet Jones, Robert A.
Franks, Sarah E.
Moorehead, Roger A.
author_sort Jones, Robert A.
collection PubMed
description Mouse models of cancer play an important role in elucidating the molecular mechanisms that contribute to tumorigenesis. The extent to which these models resemble one another and their human counterparts at the molecular level is critical in understanding tumorigenesis. In this study, we carried out a comparative gene expression analysis to generate a detailed molecular portrait of a transgenic mouse model of IGFIR-driven lung cancer. IGFIR-driven tumors displayed a strong resemblance with established mouse models of lung adenocarcinoma, particularly EGFR-driven models highlighted by elevated levels of the EGFR ligands Ereg and Areg. Cross-species analysis revealed a shared increase in human lung adenocarcinoma markers including Nkx2.1 and Napsa as well as alterations in a subset of genes with oncogenic and tumor suppressive properties such as Aurka, Ret, Klf4 and Lats2. Integrated miRNA and mRNA analysis in IGFIR-driven tumors identified interaction pairs with roles in ErbB signaling while cross-species analysis revealed coordinated expression of a subset of conserved miRNAs and their targets including miR-21-5p (Reck, Timp3 and Tgfbr3). Overall, these findings support the use of SPC-IGFIR mice as a model of human lung adenocarcinoma and provide a comprehensive knowledge base to dissect the molecular pathogenesis of tumor initiation and progression.
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spelling pubmed-62261792018-11-19 Comparative mRNA and miRNA transcriptome analysis of a mouse model of IGFIR-driven lung cancer Jones, Robert A. Franks, Sarah E. Moorehead, Roger A. PLoS One Research Article Mouse models of cancer play an important role in elucidating the molecular mechanisms that contribute to tumorigenesis. The extent to which these models resemble one another and their human counterparts at the molecular level is critical in understanding tumorigenesis. In this study, we carried out a comparative gene expression analysis to generate a detailed molecular portrait of a transgenic mouse model of IGFIR-driven lung cancer. IGFIR-driven tumors displayed a strong resemblance with established mouse models of lung adenocarcinoma, particularly EGFR-driven models highlighted by elevated levels of the EGFR ligands Ereg and Areg. Cross-species analysis revealed a shared increase in human lung adenocarcinoma markers including Nkx2.1 and Napsa as well as alterations in a subset of genes with oncogenic and tumor suppressive properties such as Aurka, Ret, Klf4 and Lats2. Integrated miRNA and mRNA analysis in IGFIR-driven tumors identified interaction pairs with roles in ErbB signaling while cross-species analysis revealed coordinated expression of a subset of conserved miRNAs and their targets including miR-21-5p (Reck, Timp3 and Tgfbr3). Overall, these findings support the use of SPC-IGFIR mice as a model of human lung adenocarcinoma and provide a comprehensive knowledge base to dissect the molecular pathogenesis of tumor initiation and progression. Public Library of Science 2018-11-09 /pmc/articles/PMC6226179/ /pubmed/30412601 http://dx.doi.org/10.1371/journal.pone.0206948 Text en © 2018 Jones et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Jones, Robert A.
Franks, Sarah E.
Moorehead, Roger A.
Comparative mRNA and miRNA transcriptome analysis of a mouse model of IGFIR-driven lung cancer
title Comparative mRNA and miRNA transcriptome analysis of a mouse model of IGFIR-driven lung cancer
title_full Comparative mRNA and miRNA transcriptome analysis of a mouse model of IGFIR-driven lung cancer
title_fullStr Comparative mRNA and miRNA transcriptome analysis of a mouse model of IGFIR-driven lung cancer
title_full_unstemmed Comparative mRNA and miRNA transcriptome analysis of a mouse model of IGFIR-driven lung cancer
title_short Comparative mRNA and miRNA transcriptome analysis of a mouse model of IGFIR-driven lung cancer
title_sort comparative mrna and mirna transcriptome analysis of a mouse model of igfir-driven lung cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226179/
https://www.ncbi.nlm.nih.gov/pubmed/30412601
http://dx.doi.org/10.1371/journal.pone.0206948
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