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The Histone Variant MacroH2A1 Impacts Circadian Gene Expression and Cell Phenotype in an In Vitro Model of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. A foremost risk factor for HCC is obesity/metabolic syndrome-related non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), which is prompted by remarkable changes in transcription patte...

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Autores principales: Carbone, Annalucia, De Santis, Elisabetta, Cela, Olga, Giambra, Vincenzo, Miele, Luca, Marrone, Giuseppe, Grieco, Antonio, Buschbeck, Marcus, Capitanio, Nazzareno, Mazza, Tommaso, Mazzoccoli, Gianluigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391426/
https://www.ncbi.nlm.nih.gov/pubmed/34440260
http://dx.doi.org/10.3390/biomedicines9081057
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author Carbone, Annalucia
De Santis, Elisabetta
Cela, Olga
Giambra, Vincenzo
Miele, Luca
Marrone, Giuseppe
Grieco, Antonio
Buschbeck, Marcus
Capitanio, Nazzareno
Mazza, Tommaso
Mazzoccoli, Gianluigi
author_facet Carbone, Annalucia
De Santis, Elisabetta
Cela, Olga
Giambra, Vincenzo
Miele, Luca
Marrone, Giuseppe
Grieco, Antonio
Buschbeck, Marcus
Capitanio, Nazzareno
Mazza, Tommaso
Mazzoccoli, Gianluigi
author_sort Carbone, Annalucia
collection PubMed
description Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. A foremost risk factor for HCC is obesity/metabolic syndrome-related non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), which is prompted by remarkable changes in transcription patterns of genes enriching metabolic, immune/inflammatory, and circadian pathways. Epigenetic mechanisms play a role in NAFLD-associated HCC, and macroH2A1, a variant of histone H2A, is involved in the pathogenesis modulating the expression of oncogenes and/or tumor suppressor genes and interacting with SIRT1, which crucially impacts the circadian clock circuitry. Hence, we aimed to appraise if and how macroH2A1 regulated the expression patterns of circadian genes in the setting of NAFLD-associated HCC. We took advantage of an in vitro model of liver cancer represented by HepG2 (human hepatocarcinoma) cells stably knocked down for macroH2A1 and conducted whole transcriptome profiling and deep phenotyping analysis. We found up-regulation of PER1 along with several deregulated circadian genes, enriching several important pathways and functions related to cancer onset and progression, such as epithelial-to-mesenchymal transition, cell cycle deregulation, and DNA damage. PER1 silencing partially mitigated the malignant phenotype induced by the loss of macroH2A1 in HCC cells. In conclusion, our findings suggest a modulatory role for the core circadian protein PER1 in liver carcinogenesis in the context of a lack of the macroH2A1 epigenetic and transcriptional landscape.
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spelling pubmed-83914262021-08-28 The Histone Variant MacroH2A1 Impacts Circadian Gene Expression and Cell Phenotype in an In Vitro Model of Hepatocellular Carcinoma Carbone, Annalucia De Santis, Elisabetta Cela, Olga Giambra, Vincenzo Miele, Luca Marrone, Giuseppe Grieco, Antonio Buschbeck, Marcus Capitanio, Nazzareno Mazza, Tommaso Mazzoccoli, Gianluigi Biomedicines Article Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. A foremost risk factor for HCC is obesity/metabolic syndrome-related non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), which is prompted by remarkable changes in transcription patterns of genes enriching metabolic, immune/inflammatory, and circadian pathways. Epigenetic mechanisms play a role in NAFLD-associated HCC, and macroH2A1, a variant of histone H2A, is involved in the pathogenesis modulating the expression of oncogenes and/or tumor suppressor genes and interacting with SIRT1, which crucially impacts the circadian clock circuitry. Hence, we aimed to appraise if and how macroH2A1 regulated the expression patterns of circadian genes in the setting of NAFLD-associated HCC. We took advantage of an in vitro model of liver cancer represented by HepG2 (human hepatocarcinoma) cells stably knocked down for macroH2A1 and conducted whole transcriptome profiling and deep phenotyping analysis. We found up-regulation of PER1 along with several deregulated circadian genes, enriching several important pathways and functions related to cancer onset and progression, such as epithelial-to-mesenchymal transition, cell cycle deregulation, and DNA damage. PER1 silencing partially mitigated the malignant phenotype induced by the loss of macroH2A1 in HCC cells. In conclusion, our findings suggest a modulatory role for the core circadian protein PER1 in liver carcinogenesis in the context of a lack of the macroH2A1 epigenetic and transcriptional landscape. MDPI 2021-08-20 /pmc/articles/PMC8391426/ /pubmed/34440260 http://dx.doi.org/10.3390/biomedicines9081057 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Carbone, Annalucia
De Santis, Elisabetta
Cela, Olga
Giambra, Vincenzo
Miele, Luca
Marrone, Giuseppe
Grieco, Antonio
Buschbeck, Marcus
Capitanio, Nazzareno
Mazza, Tommaso
Mazzoccoli, Gianluigi
The Histone Variant MacroH2A1 Impacts Circadian Gene Expression and Cell Phenotype in an In Vitro Model of Hepatocellular Carcinoma
title The Histone Variant MacroH2A1 Impacts Circadian Gene Expression and Cell Phenotype in an In Vitro Model of Hepatocellular Carcinoma
title_full The Histone Variant MacroH2A1 Impacts Circadian Gene Expression and Cell Phenotype in an In Vitro Model of Hepatocellular Carcinoma
title_fullStr The Histone Variant MacroH2A1 Impacts Circadian Gene Expression and Cell Phenotype in an In Vitro Model of Hepatocellular Carcinoma
title_full_unstemmed The Histone Variant MacroH2A1 Impacts Circadian Gene Expression and Cell Phenotype in an In Vitro Model of Hepatocellular Carcinoma
title_short The Histone Variant MacroH2A1 Impacts Circadian Gene Expression and Cell Phenotype in an In Vitro Model of Hepatocellular Carcinoma
title_sort histone variant macroh2a1 impacts circadian gene expression and cell phenotype in an in vitro model of hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391426/
https://www.ncbi.nlm.nih.gov/pubmed/34440260
http://dx.doi.org/10.3390/biomedicines9081057
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