EZH1/2 inhibition augments the anti-tumor effects of sorafenib in hepatocellular carcinoma.

Aged Animals Antineoplastic Agents / therapeutic use Benzamides / therapeutic use Carcinoma, Hepatocellular / genetics Cell Line, Tumor Down-Regulation / drug effects Enhancer of Zeste Homolog 2 Protein / antagonists & inhibitors Female Genetic Therapy Humans Indazoles / therapeutic use Liver Neoplasms / genetics Male Mice, SCID Middle Aged Piperazines / therapeutic use Polycomb Repressive Complex 2 / antagonists & inhibitors Pyridones / therapeutic use Sorafenib / therapeutic use

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
01 11 2021
Historique:
received: 25 06 2021
accepted: 12 10 2021
entrez: 2 11 2021
pubmed: 3 11 2021
medline: 27 1 2022
Statut: epublish

Résumé

Both EZH2 and its homolog EZH1 function as histone H3 Lysine 27 (H3K27) methyltransferases and repress the transcription of target genes. Dysregulation of H3K27 trimethylation (H3K27me3) plays an important role in the development and progression of cancers such as hepatocellular carcinoma (HCC). This study investigated the relationship between the expression of EZH1/2 and the level of H3K27me3 in HCC. Additionally, the role of EZH1/2 in cell growth, tumorigenicity, and resistance to sorafenib were also analyzed. Both the lentiviral knockdown and the pharmacological inhibition of EZH1/2 (UNC1999) diminished the level of H3K27me3 and suppressed cell growth in liver cancer cells, compared with EZH1 or EZH2 single knockdown. Although a significant association was observed between EZH2 expression and H3K27me3 levels in HCC samples, overexpression of EZH1 appeared to contribute to enhanced H3K27me3 levels in some EZH2

Identifiants

DOI: 10.1038/s41598-021-00889-0 PMID: 34725436 PMC: PMC8560765
pubmed: 34725436
doi: 10.1038/s41598-021-00889-0
pii: 10.1038/s41598-021-00889-0
pmc: PMC8560765
doi:

Substances chimiques

Antineoplastic Agents 0
Benzamides 0
Indazoles 0
Piperazines 0
Pyridones 0
UNC1999 0
Sorafenib 9ZOQ3TZI87
EZH1 protein, human EC 2.1.1.43
EZH2 protein, human EC 2.1.1.43
Enhancer of Zeste Homolog 2 Protein EC 2.1.1.43
Polycomb Repressive Complex 2 EC 2.1.1.43

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

21396

Subventions

Organisme : Japan Society for the Promotion of Science
ID : JP19K17482
Organisme : Japan Agency for Medical Research and Development
ID : #JP20fk0210054

Informations de copyright

© 2021. The Author(s).

Références

N Engl J Med. 2008 Jul 24;359(4):378-90
pubmed: 18650514
Cell. 2012 Jul 6;150(1):12-27
pubmed: 22770212
Int J Cancer. 2015 Mar 1;136(5):E359-86
pubmed: 25220842
Cancer Res Treat. 2014 Jul;46(3):209-22
pubmed: 25038756
Nature. 2012 Dec 6;492(7427):108-12
pubmed: 23051747
N Engl J Med. 2008 Mar 13;358(11):1148-59
pubmed: 18337604
Int J Cancer. 2012 Jun 1;130(11):2557-67
pubmed: 21717453
Lancet. 2017 Jan 7;389(10064):56-66
pubmed: 27932229
Science. 2005 Oct 14;310(5746):306-10
pubmed: 16224021
Expert Opin Ther Pat. 2017 Jul;27(7):797-813
pubmed: 28394193
Hepatology. 2012 Aug;56(2):622-31
pubmed: 22370893
Nat Rev Cancer. 2014 Nov;14(11):747-53
pubmed: 25253389
Cancer Res. 2017 Dec 1;77(23):6651-6666
pubmed: 28978636
Lancet. 2003 Dec 6;362(9399):1907-17
pubmed: 14667750
Mol Cell. 2008 Nov 21;32(4):491-502
pubmed: 19026780
Cell Stem Cell. 2010 Sep 3;7(3):299-313
pubmed: 20804967
J Hepatocell Carcinoma. 2016 Oct 05;3:41-53
pubmed: 27785449
Nature. 2011 Jan 20;469(7330):343-9
pubmed: 21248841
Blood. 2015 Sep 3;126(10):1172-83
pubmed: 26219303
Cancer Cell. 2013 Jun 10;23(6):839-52
pubmed: 23684459
Nat Rev Genet. 2016 Aug;17(8):487-500
pubmed: 27346641
Mol Med. 2011 Jan-Feb;17(1-2):12-20
pubmed: 20844838
Mol Cell. 2018 Jan 18;69(2):279-291.e5
pubmed: 29351847
Nature. 2014 Oct 9;514(7521):247-51
pubmed: 25119042
Biomark Res. 2018 Mar 9;6:10
pubmed: 29556394
Nat Protoc. 2008;3(6):1101-8
pubmed: 18546601
Lancet. 2018 Mar 24;391(10126):1163-1173
pubmed: 29433850
Adv Enzyme Regul. 1984;22:27-55
pubmed: 6382953
FASEB J. 2015 May;29(5):1653-62
pubmed: 25477280
Mol Cell. 2014 Jun 5;54(5):716-27
pubmed: 24905005
Science. 2012 Dec 14;338(6113):1465-9
pubmed: 23239736
ACS Chem Biol. 2013;8(6):1324-34
pubmed: 23614352
PLoS One. 2014 Mar 10;9(3):e91330
pubmed: 24614346
Cancer Cell. 2017 Feb 13;31(2):286-299
pubmed: 28196596
Int J Mol Sci. 2015 Nov 13;16(11):27107-32
pubmed: 26580594
Hepatol Res. 2019 Jan;49(1):3-13
pubmed: 30238570
Cell Stem Cell. 2014 Jun 5;14(6):735-51
pubmed: 24905164
Cell Stem Cell. 2012 Nov 2;11(5):649-62
pubmed: 23122289
Mol Cell. 2008 Nov 21;32(4):503-18
pubmed: 19026781
Nat Med. 2017 Jan;23(1):69-78
pubmed: 27941792

Auteurs

Yuko Kusakabe (Y)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Tetsuhiro Chiba (T)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. chibat@chiba-u.jp.

Motohiko Oshima (M)

Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokenadai, Minato-ku, Tokyo, 108-8639, Japan.
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Shuhei Koide (S)

Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokenadai, Minato-ku, Tokyo, 108-8639, Japan.
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Ola Rizq (O)

Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokenadai, Minato-ku, Tokyo, 108-8639, Japan.
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Kazumasa Aoyama (K)

Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Junjie Ao (J)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Tatsuya Kaneko (T)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Hiroaki Kanzaki (H)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Kengo Kanayama (K)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Takahiro Maeda (T)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Tomoko Saito (T)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Ryo Nakagawa (R)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Kazufumi Kobayashi (K)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Soichiro Kiyono (S)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Masato Nakamura (M)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Sadahisa Ogasawara (S)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Eiichiro Suzuki (E)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Shingo Nakamoto (S)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Shin Yasui (S)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Rintaro Mikata (R)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Ryosuke Muroyama (R)

Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Tatsuo Kanda (T)

Department of Gastroenterology and Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.

Hitoshi Maruyama (H)

Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-08421, Japan.

Jun Kato (J)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Naoya Mimura (N)

Department of Transfusion Medicine and Cell Therapy, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Anqi Ma (A)

Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Jian Jin (J)

Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Yoh Zen (Y)

Institute of Liver Studies, King's College Hospital, London, UK.

Masayuki Otsuka (M)

Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Atsushi Kaneda (A)

Department of Molecular Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Atsushi Iwama (A)

Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokenadai, Minato-ku, Tokyo, 108-8639, Japan.
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Naoya Kato (N)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Eucaryotes › Animaux › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Benzoates › Benzamides › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › Carcinome hépatocellulaire › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation négative › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Protéines du groupe Polycomb › Complexe répresseur Polycomb-2 › Protéine-2 homologue de l'activateur de Zeste › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Thérapie génétique › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Indazoles › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris SCID › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pipérazines › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Protéines du groupe Polycomb › Complexe répresseur Polycomb-2 › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Pyridones › EZH1/2 inhibition augments the anti-tumor...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Acides nicotiniques › Nicotinamide › Sorafénib › EZH1/2 inhibition augments the anti-tumor...