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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...

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Autores principales: García-Chávez, J. Noé, Vásquez-Garzón, Verónica R., López, Mercedes G., Villa-Treviño, Saúl, Montiel, Rafael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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.
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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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