Bromodomain-containing protein BRPF1 is a therapeutic target for liver cancer.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
20 07 2021
20 07 2021
Historique:
received:
27
08
2020
accepted:
30
06
2021
entrez:
21
7
2021
pubmed:
22
7
2021
medline:
12
11
2021
Statut:
epublish
Résumé
Epigenetic deregulation plays an essential role in hepatocellular carcinoma (HCC) progression. Bromodomains are epigenetic "readers" of histone acetylation. Recently, bromodomain inhibitors have exhibited promising therapeutic potential for cancer treatment. Using transcriptome sequencing, we identified BRPF1 (bromodomain and PHD finger containing 1) as the most significantly upregulated gene among the 43 bromodomain-containing genes in human HCC. BRPF1 upregulation was significantly associated with poor patient survival. Gene ablation or pharmacological inactivation of BRPF1 significantly attenuated HCC cell growth in vitro and in vivo. BRPF1 was involved in cell cycle progression, senescence and cancer stemness. Transcriptome sequencing revealed that BRPF1 is a master regulator controlling the expression of multiple key oncogenes, including E2F2 and EZH2. We demonstrated that BRPF1 activated E2F2 and EZH2 expression by facilitating promoter H3K14 acetylation through MOZ/MORF complex. In conclusion, BRPF1 is frequently upregulated in human HCCs. Targeting BRPF1 may be an approach for HCC treatment.
Identifiants
pubmed: 34285329
doi: 10.1038/s42003-021-02405-6
pii: 10.1038/s42003-021-02405-6
pmc: PMC8292510
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
BRPF1 protein, human
0
DNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
888Informations de copyright
© 2021. The Author(s).
Références
Nat Commun. 2018 Dec 3;9(1):5139
pubmed: 30510198
Leukemia. 2005 Dec;19(12):2344-5
pubmed: 16193081
Gut. 2021 Jan;70(1):157-169
pubmed: 32217639
Cell Stem Cell. 2019 Jan 3;24(1):25-40
pubmed: 30595497
Hepatology. 2019 May;69(5):2013-2030
pubmed: 30516846
Nat Rev Drug Discov. 2006 Jan;5(1):37-50
pubmed: 16485345
FEBS J. 2015 Jan;282(2):224-58
pubmed: 25393971
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Mol Cell. 2001 Jul;8(1):105-13
pubmed: 11511364
Biochim Biophys Acta. 2015 Aug;1853(8):1818-26
pubmed: 25920810
N Engl J Med. 2008 Jul 24;359(4):378-90
pubmed: 18650514
Cell. 2011 Sep 16;146(6):904-17
pubmed: 21889194
J Gastrointest Cancer. 2017 Sep;48(3):238-240
pubmed: 28626852
J Hepatocell Carcinoma. 2019 Jan 31;6:31-39
pubmed: 30775342
Oncogene. 2016 Sep 8;35(36):4689-97
pubmed: 26804177
Clin Mol Hepatol. 2016 Sep;22(3):309-318
pubmed: 27729631
Genes Chromosomes Cancer. 2000 Jun;28(2):138-44
pubmed: 10824998
Sci Adv. 2020 Jan 22;6(4):eaax0021
pubmed: 32010779
Hepatology. 2019 Jun;69(6):2502-2517
pubmed: 30723918
Clin Liver Dis. 2015 May;19(2):223-38
pubmed: 25921660
Biochem J. 2007 Mar 15;402(3):559-66
pubmed: 17083329
Am J Hum Genet. 2017 Jan 5;100(1):91-104
pubmed: 27939640
Oncologist. 2009 Jan;14(1):95-100
pubmed: 19144678
Br J Cancer. 2014 Mar 4;110(5):1189-98
pubmed: 24518598
Oncogene. 2002 Apr 18;21(17):2729-40
pubmed: 11965546
Oncotarget. 2016 Jan 19;7(3):2462-74
pubmed: 26575167
Hepatology. 2013 Feb;57(2):637-47
pubmed: 22991213
Cell. 2006 Apr 21;125(2):301-13
pubmed: 16630818
Nat Genet. 2014 Dec;46(12):1267-73
pubmed: 25362482
Cancer. 2006 Apr 15;106(8):1794-803
pubmed: 16532500
Cancer Cell. 2014 Mar 17;25(3):393-405
pubmed: 24651015
Nat Rev Mol Cell Biol. 2015 Apr;16(4):258-64
pubmed: 25549891
Nat Commun. 2019 Oct 17;10(1):4724
pubmed: 31624313
J Clin Oncol. 2018 Oct 20;36(30):3007-3014
pubmed: 29733771
Dev Cell. 2009 Nov;17(5):674-86
pubmed: 19922872
Int J Mol Sci. 2016 Nov 07;17(11):
pubmed: 27827996
N Engl J Med. 2018 Jul 05;379(1):54-63
pubmed: 29972759
Mol Cell Biol. 2008 Nov;28(22):6828-43
pubmed: 18794358
J Hepatol. 2017 Aug;67(2):302-309
pubmed: 28336466
Hepatology. 2016 Feb;63(2):474-87
pubmed: 26481868
ACS Chem Biol. 2017 Oct 20;12(10):2619-2630
pubmed: 28849908
Clin Cancer Res. 2019 Nov 1;25(21):6309-6319
pubmed: 31420359
Genes Dev. 2012 Jun 15;26(12):1376-91
pubmed: 22713874
Nature. 2010 Dec 23;468(7327):1067-73
pubmed: 20871596
Lancet. 2017 Jan 7;389(10064):56-66
pubmed: 27932229
Science. 2017 Jul 21;357(6348):
pubmed: 28729483
Oncotarget. 2015 Oct 20;6(32):33623-35
pubmed: 26378038
Cell Rep. 2017 Feb 28;18(9):2162-2174
pubmed: 28249162
Bioinformatics. 2012 Aug 15;28(16):2205-6
pubmed: 22718786
Hepatology. 2012 Aug;56(2):622-31
pubmed: 22370893
Mol Cell. 2016 Apr 21;62(2):169-180
pubmed: 27105113
J Clin Invest. 2016 Sep 1;126(9):3247-62
pubmed: 27500495
Int J Hematol. 2014 Jan;99(1):21-31
pubmed: 24258712
World J Hepatol. 2013 Jul 27;5(7):345-52
pubmed: 23898367
Lancet Haematol. 2016 Apr;3(4):e186-95
pubmed: 27063977
Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8758-63
pubmed: 12840145
Semin Liver Dis. 1999;19(3):311-22
pubmed: 10518310
J Hepatol. 2017 Oct;67(4):758-769
pubmed: 28532996
J Biol Chem. 2015 Mar 13;290(11):7114-29
pubmed: 25568313
Cell Rep. 2019 Dec 17;29(12):4036-4052.e10
pubmed: 31851932
Epigenetics. 2014 Feb;9(2):186-93
pubmed: 24169304
Cancer Res. 2017 Jun 1;77(11):2976-2989
pubmed: 28416490
Cell Rep. 2016 Sep 13;16(11):2829-2837
pubmed: 27626654