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Integration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma
Mitochondria participate in multiple functions in eukaryotic cells. Although disruption of mitochondrial function has been associated with energetic deregulation in cancer, the chronological changes in mitochondria during cancer development remain unclear. With the aim to assess the role of mitochon...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360386/ https://www.ncbi.nlm.nih.gov/pubmed/34383828 http://dx.doi.org/10.1371/journal.pone.0256016 |
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author | García-Chávez, J. Noé Vásquez-Garzón, Verónica R. López, Mercedes G. Villa-Treviño, Saúl Montiel, Rafael |
author_facet | García-Chávez, J. Noé Vásquez-Garzón, Verónica R. López, Mercedes G. Villa-Treviño, Saúl Montiel, Rafael |
author_sort | García-Chávez, J. Noé |
collection | PubMed |
description | Mitochondria participate in multiple functions in eukaryotic cells. Although disruption of mitochondrial function has been associated with energetic deregulation in cancer, the chronological changes in mitochondria during cancer development remain unclear. With the aim to assess the role of mitochondria throughout cancer development, we analyzed samples chronologically obtained from induced hepatocellular carcinoma (HCC) in rats. In our analyses, we integrated mitochondrial proteomic data, mitochondrial metabolomic data and nuclear genome transcriptomic data. We used pathway over-representation and weighted gene co-expression network analysis (WGCNA) to integrate expression profiles of genes, miRNAs, proteins and metabolite levels throughout HCC development. Our results show that mitochondria are dynamic organelles presenting specific modifications in different stages of HCC development. We also found that mitochondrial proteomic profiles from tissues adjacent to nodules or tumor are determined more by the stage of HCC development than by tissue type, and we evaluated two models to predict HCC stage of the samples using proteomic profiles. Finally, we propose an omics integration pipeline to massively identify molecular features that could be further evaluated as key regulators, biomarkers or therapeutic targets. As an example, we show a group of miRNAs and transcription factors as candidates, responsible for mitochondrial metabolic modification in HCC. |
format | Online Article Text |
id | pubmed-8360386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-83603862021-08-13 Integration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma García-Chávez, J. Noé Vásquez-Garzón, Verónica R. López, Mercedes G. Villa-Treviño, Saúl Montiel, Rafael PLoS One Research Article Mitochondria participate in multiple functions in eukaryotic cells. Although disruption of mitochondrial function has been associated with energetic deregulation in cancer, the chronological changes in mitochondria during cancer development remain unclear. With the aim to assess the role of mitochondria throughout cancer development, we analyzed samples chronologically obtained from induced hepatocellular carcinoma (HCC) in rats. In our analyses, we integrated mitochondrial proteomic data, mitochondrial metabolomic data and nuclear genome transcriptomic data. We used pathway over-representation and weighted gene co-expression network analysis (WGCNA) to integrate expression profiles of genes, miRNAs, proteins and metabolite levels throughout HCC development. Our results show that mitochondria are dynamic organelles presenting specific modifications in different stages of HCC development. We also found that mitochondrial proteomic profiles from tissues adjacent to nodules or tumor are determined more by the stage of HCC development than by tissue type, and we evaluated two models to predict HCC stage of the samples using proteomic profiles. Finally, we propose an omics integration pipeline to massively identify molecular features that could be further evaluated as key regulators, biomarkers or therapeutic targets. As an example, we show a group of miRNAs and transcription factors as candidates, responsible for mitochondrial metabolic modification in HCC. Public Library of Science 2021-08-12 /pmc/articles/PMC8360386/ /pubmed/34383828 http://dx.doi.org/10.1371/journal.pone.0256016 Text en © 2021 García-Chávez et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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 García-Chávez, J. Noé Vásquez-Garzón, Verónica R. López, Mercedes G. Villa-Treviño, Saúl Montiel, Rafael Integration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma |
title | Integration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma |
title_full | Integration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma |
title_fullStr | Integration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma |
title_full_unstemmed | Integration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma |
title_short | Integration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma |
title_sort | integration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360386/ https://www.ncbi.nlm.nih.gov/pubmed/34383828 http://dx.doi.org/10.1371/journal.pone.0256016 |
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