Differentiation Therapy by Epigenetic Reconditioning Exerts Antitumor Effects on Liver Cancer Cells

Molecular Therapy : the Journal of the American Society of Gene Therapy
Luc GailhousteTakahiro Ochiya

Abstract

Primary liver tumors are mainly represented by hepatocellular carcinoma (HCC), one of the most aggressive and resistant forms of cancer. Liver tumorigenesis is characterized by an accumulation of epigenetic abnormalities, leading to gene extinction and loss of hepatocyte differentiation. The aim of this work was to investigate the feasibility of converting liver cancer cells toward a less aggressive and differentiated phenotype using a process called epigenetic reconditioning. Here, we showed that an epigenetic regimen with non-cytotoxic doses of the demethylating compound 5-azacytidine (5-AZA) promoted an anti-cancer response by inhibiting HCC cell tumorigenicity. Furthermore, epigenetic reconditioning improved sorafenib response. Remarkably, epigenetic treatment was associated with a significant restoration of differentiation, as attested by the increased expression of characteristic hepatocyte markers in reconditioned cells. In particular, we showed that reexpression of these epigenetically silenced liver genes following 5-AZA treatment or after knockdown of DNA methyltransferase 1 (DNMT1) was the result of regional CpG demethylation. Lastly, we confirmed the efficacy of HCC differentiation therapy by epigenetic reconditioni...Continue Reading

Citations

May 6, 2019·Clinical and Translational Medicine·Tan Boon TohEdward Kai-Hua Chow
Dec 24, 2018·International Journal of Molecular Sciences·Christoph OingFriedemann Honecker
Sep 22, 2019·Journal of the American Society of Nephrology : JASN·Michael S Goligorsky
Jun 14, 2020·Signal Transduction and Targeted Therapy·Weiwei TangXuehao Wang
Dec 2, 2020·International Journal of Molecular Sciences·Pradeep Kumar RajanJuan Sanabria
Jun 25, 2020·Cell Reports·Yan ChengZeng-Jie Yang
Dec 11, 2020·BioMed Research International·Mohamed H YousefAnwar Abdelnaser
Mar 2, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Fatemeh ZolghadrNaisana Seyedasli
Apr 6, 2021·Current Hepatology Reports·Adeniji Nia, Renumathy Dhanasekaran
Jun 4, 2021·Cell Death Discovery·Luc GailhousteYutaka Furutani
Jul 30, 2021·Seminars in Cancer Biology·Ganji Purnachandra NagarajuBassel F El-Rayes
Aug 24, 2021·Journal of Cellular and Molecular Medicine·Bahare ShokoohianMassoud Vosough

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Methods Mentioned

BETA
surgical resection
xenograft
ELISA
transfection
biopsies
methylation profiling
PCR
Assay

Software Mentioned

MethPrimer
ImageJ
COBRA
MedCalc

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