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: J Noé García-Chávez, Verónica R Vásquez-Garzón, Mercedes G López, Saúl Villa-Treviño, Rafael Montiel
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/ceb83fbd4f8c4f0d8f06a95ed5b310ea
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spelling oai:doaj.org-article:ceb83fbd4f8c4f0d8f06a95ed5b310ea2021-12-02T20:18:16ZIntegration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma.1932-620310.1371/journal.pone.0256016https://doaj.org/article/ceb83fbd4f8c4f0d8f06a95ed5b310ea2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256016https://doaj.org/toc/1932-6203Mitochondria 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.J Noé García-ChávezVerónica R Vásquez-GarzónMercedes G LópezSaúl Villa-TreviñoRafael MontielPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0256016 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
J Noé García-Chávez
Verónica R Vásquez-Garzón
Mercedes G López
Saúl Villa-Treviño
Rafael Montiel
Integration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma.
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 article
author J Noé García-Chávez
Verónica R Vásquez-Garzón
Mercedes G López
Saúl Villa-Treviño
Rafael Montiel
author_facet J Noé García-Chávez
Verónica R Vásquez-Garzón
Mercedes G López
Saúl Villa-Treviño
Rafael Montiel
author_sort J Noé García-Chávez
title 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_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_sort integration of chronological omics data reveals mitochondrial regulatory mechanisms during the development of hepatocellular carcinoma.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/ceb83fbd4f8c4f0d8f06a95ed5b310ea
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AT veronicarvasquezgarzon integrationofchronologicalomicsdatarevealsmitochondrialregulatorymechanismsduringthedevelopmentofhepatocellularcarcinoma
AT mercedesglopez integrationofchronologicalomicsdatarevealsmitochondrialregulatorymechanismsduringthedevelopmentofhepatocellularcarcinoma
AT saulvillatrevino integrationofchronologicalomicsdatarevealsmitochondrialregulatorymechanismsduringthedevelopmentofhepatocellularcarcinoma
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