DNA Hypomethylation and Histone Variant macroH2A1 Synergistically Attenuate Chemotherapy-Induced Senescence to Promote Hepatocellular Carcinoma Progression

Cancer Research
Michela BorghesanManlio Vinciguerra

Abstract

Aging is a major risk factor for progression of liver diseases to hepatocellular carcinoma (HCC). Cellular senescence contributes to age-related tissue dysfunction, but the epigenetic basis underlying drug-induced senescence remains unclear. macroH2A1, a variant of histone H2A, is a marker of senescence-associated heterochromatic foci that synergizes with DNA methylation to silence tumor-suppressor genes in human fibroblasts. In this study, we investigated the relationship between macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, and liver carcinogenesis. We found that protein levels of both macroH2A1 isoforms were increased in the livers of very elderly rodents and humans, and were robust immunohistochemical markers of human cirrhosis and HCC. In response to the chemotherapeutic and DNA-demethylating agent 5-aza-deoxycytidine (5-aza-dC), transgenic expression of macroH2A1 isoforms in HCC cell lines prevented the emergence of a senescent-like phenotype and induced synergistic global DNA hypomethylation. Conversely, macroH2A1 depletion amplified the antiproliferative effects of 5-aza-dC in HCC cells, but failed to enhance senescence. Senescence-associated secretory phenotype and whole-transcriptome analyses implicated the ...Continue Reading

References

May 26, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·David E KleinerUNKNOWN Nonalcoholic Steatohepatitis Clinical Research Network
Jun 21, 2005·Nature Structural & Molecular Biology·Georg KustatscherAndreas G Ladurner
Jun 2, 2006·Molecular and Cellular Biology·Lakshmi N Changolkar, John R Pehrson
Jan 24, 2007·Molecular and Cellular Biology·Lakshmi N ChangolkarJohn R Pehrson
Jul 20, 2007·Methods in Molecular Biology·Koji ItahanaGoberdhan P Dimri
Aug 25, 2007·The Journal of Clinical Investigation·Diego F CalvisiSnorri S Thorgeirsson
Nov 14, 2007·Epigenetics : Official Journal of the DNA Methylation Society·Mohsen KarimiTomas J Ekström
Apr 3, 2010·Epigenetics & Chromatin·Mathieu BoulardPhilippe Bouvet
Oct 13, 2010·Molecular and Cellular Biology·Lakshmi N ChangolkarJohn R Pehrson
Dec 24, 2010·Aging Cell·Jill A KreilingJohn M Sedivy
Aug 16, 2011·Biochimica Et Biophysica Acta·Taranjit Singh Rai, Peter D Adams
Aug 17, 2011·Molecular and Cellular Biology·Leonid NovikovMatthew J Gamble
Mar 28, 2012·Epigenomics·Catherine CreppeMarcus Buschbeck
Apr 25, 2012·Digestive Diseases and Sciences·Giorgia BenegiamoValerio Pazienza
Mar 5, 2013·The Journal of Clinical Investigation·Tamara TchkoniaJames L Kirkland
Mar 5, 2013·Cellular and Molecular Life Sciences : CMLS·Melanija PosavecMarcus Buschbeck
Mar 28, 2013·Cancer Letters·Neus CantariñoMarcus Buschbeck
Jul 3, 2013·Aging Cell·Fareeba SheedfarManlio Vinciguerra
Sep 28, 2013·Nucleic Acids Research·Rong CongPhilippe Bouvet
May 23, 2014·International Journal of Obesity : Journal of the International Association for the Study of Obesity·F SheedfarM Vinciguerra
Sep 19, 2014·Biochemical Society Transactions·Michela BorghesanManlio Vinciguerra
Sep 24, 2014·Nature Reviews. Gastroenterology & Hepatology·Gregory J Gores
Oct 15, 2014·Proceedings of the National Academy of Sciences of the United States of America·Steve HorvathJochen Hampe
Dec 21, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christine PodriniAzzura Greco

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Citations

Sep 21, 2016·Epigenetics : Official Journal of the DNA Methylation Society·Simone JueligerManlio Vinciguerra
Nov 2, 2016·Epigenetics & Chromatin·Valerio PazienzaManlio Vinciguerra
Nov 14, 2016·Carcinogenesis·Chinthalapally V RaoHiroshi Y Yamada
Feb 2, 2017·Nature Reviews. Molecular Cell Biology·Marcus Buschbeck, Sandra B Hake
Sep 1, 2018·Epigenetics : Official Journal of the DNA Methylation Society·Oriana Lo ReManlio Vinciguerra
May 18, 2019·Cancers·Sebastiano GiallongoManlio Vinciguerra
Sep 16, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Oriana Lo ReManlio Vinciguerra
Sep 14, 2019·Cell Proliferation·Kristina Kovacovicova, Manlio Vinciguerra
Nov 14, 2019·Cancers·Gianluigi MazzoccoliAntonio Grieco
Jun 6, 2019·Cancer Cell International·Tânia Soraia Vieira-SilvaCarmen Jerónimo
May 20, 2020·Journal of Cellular and Molecular Medicine·Bi-Lan Li, Xiao-Ping Wan
Jun 23, 2020·Antioxidants & Redox Signaling·Sebastiano GiallongoManlio Vinciguerra
Jul 30, 2020·Medicina·Andrea Maugeri, Martina Barchitta
May 22, 2019·The Journal of Cell Biology·Hanae SatoJohn M Greally
Jan 21, 2017·BioMed Research International·Mankgopo M KgatleHenry N Hairwadzi
Oct 30, 2020·Frontiers in Cell and Developmental Biology·Juan Li, Ying Zhu
Dec 2, 2020·Journal of Cellular and Molecular Medicine·Jiannan TuShengchi Chen
Feb 12, 2021·Nature Reviews. Cancer·Flávia G GhiraldiniEmily Bernstein
Mar 9, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Jan FrohlichManlio Vinciguerra
Apr 4, 2021·International Journal of Molecular Sciences·Abhishek Chandra, Jyotika Rajawat
Apr 10, 2021·Cell Communication and Signaling : CCS·Marco RaffaeleManlio Vinciguerra
Jul 3, 2021·Cancers·Chen-Jen HsuFlorian H Heidel
Jul 31, 2021·Journal of Experimental & Clinical Cancer Research : CR·Daniel Otero-Albiol, Amancio Carnero
Jul 29, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Valentina ChiodiManlio Vinciguerra

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