The HPSE Gene Insulator-A Novel Regulatory Element That Affects Heparanase Expression, Stem Cell Mobilization, and the Risk of Acute Graft versus Host Disease.
HPSE gene
SNPs
acute GVHD
allogeneic HSCT
enhancer
insulator
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
23 09 2021
23 09 2021
Historique:
received:
20
07
2021
revised:
14
09
2021
accepted:
17
09
2021
entrez:
23
10
2021
pubmed:
24
10
2021
medline:
15
12
2021
Statut:
epublish
Résumé
The HPSE gene encodes heparanase (HPSE), a key player in cancer, inflammation, and autoimmunity. We have previously identified a strong HPSE gene enhancer involved in self-regulation of heparanase by negative feedback exerted in a functional rs4693608 single-nucleotide polymorphism (SNP) dependent manner. In the present study, we analyzed the HPSE gene insulator region, located in intron 9 and containing rs4426765, rs28649799, and rs4364254 SNPs. Our results indicate that this region exhibits HPSE regulatory activity. SNP substitutions lead to modulation of a unique DNA-protein complex that affects insulator activity. Analysis of interactions between enhancer and insulator SNPs revealed that rs4693608 has a major effect on HPSE expression and the risk of post-transplantation acute graft versus host disease (GVHD). The C alleles of insulator SNPs rs4364254 and rs4426765 modify the activity of the HPSE enhancer, resulting in altered HPSE expression and increased risk of acute GVHD. Moreover, rs4426765 correlated with HPSE expression in activated mononuclear cells, as well as with CD3 levels and lymphocyte counts following G-CSF mobilization. rs4363084 and rs28649799 were found to be associated with CD34
Identifiants
pubmed: 34685503
pii: cells10102523
doi: 10.3390/cells10102523
pmc: PMC8534152
pii:
doi:
Substances chimiques
heparanase
EC 3.2.1.-
Glucuronidase
EC 3.2.1.31
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Israel Science Foundation
ID : ISF grant 1021/19
Références
Adv Exp Med Biol. 2020;1221:231-249
pubmed: 32274712
J Biol Chem. 2002 Mar 15;277(11):8989-98
pubmed: 11779847
Acta Haematol. 2007;117(1):57-64
pubmed: 17095861
J Cancer Res Clin Oncol. 2015 May;141(5):877-85
pubmed: 25335953
Cancers (Basel). 2021 Jun 13;13(12):
pubmed: 34199150
Sci Rep. 2021 Jun 10;11(1):12265
pubmed: 34112915
Adv Exp Med Biol. 2020;1221:331-349
pubmed: 32274716
Cancer Res. 2003 Dec 15;63(24):8821-6
pubmed: 14695198
Diabetes. 2005 Jul;54(7):2172-8
pubmed: 15983219
Breast Dis. 2006-2007;26:157-62
pubmed: 17473374
Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):E4428-37
pubmed: 26216945
Nat Rev Drug Discov. 2020 Nov;19(11):757-775
pubmed: 33020616
Clin Cancer Res. 2005 Feb 1;11(3):1028-36
pubmed: 15709168
Int J Mol Sci. 2021 May 18;22(10):
pubmed: 34156395
Curr Stem Cell Res Ther. 2006 May;1(2):189-201
pubmed: 18220866
J Leukoc Biol. 2014 Apr;95(4):677-88
pubmed: 24319286
Matrix Biol. 2013 Jun 24;32(5):228-33
pubmed: 23499527
Oncogenesis. 2018 Jun 29;7(6):51
pubmed: 29955035
Stat Med. 1999 Mar 30;18(6):695-706
pubmed: 10204198
Biomol Concepts. 2015 Dec;6(5-6):415-21
pubmed: 26552066
J Leukoc Biol. 2009 Aug;86(2):445-55
pubmed: 19406828
Sci Rep. 2016 Sep 06;6:32628
pubmed: 27595937
Oncogene. 2003 Oct 30;22(49):7737-49
pubmed: 14586400
PLoS One. 2014 Mar 14;9(3):e92190
pubmed: 24632672
Leukemia. 2007 Nov;21(11):2296-303
pubmed: 17611567
Biol Blood Marrow Transplant. 2009 Oct;15(10):1143-238
pubmed: 19747629
Adv Exp Med Biol. 2020;1221:189-229
pubmed: 32274711
Clin Cancer Res. 2008 Feb 1;14(3):668-76
pubmed: 18212251
Drug Resist Updat. 2016 Nov;29:54-75
pubmed: 27912844
Theranostics. 2014 Jan 23;4(3):280-9
pubmed: 24505236
Int J Biochem Cell Biol. 2006;38(12):2018-39
pubmed: 16901744
Adv Exp Med Biol. 2020;1221:71-96
pubmed: 32274707
J Transl Med. 2020 Nov 30;18(1):453
pubmed: 33256730
Atherosclerosis. 2019 Apr;283:124-126
pubmed: 30745229
Nat Rev Nephrol. 2017 Apr;13(4):201-212
pubmed: 28163306
Trends Biochem Sci. 2018 Jan;43(1):18-31
pubmed: 29162390
Cancer Res. 2011 Feb 1;71(3):645-54
pubmed: 21266359
Genes (Basel). 2015 Sep 01;6(3):790-811
pubmed: 26340639
Transplantation. 1974 Oct;18(4):295-304
pubmed: 4153799
Genes Dev. 2002 Feb 1;16(3):271-88
pubmed: 11825869
J Clin Med. 2021 May 18;10(10):
pubmed: 34070058
J Biol Chem. 2003 Dec 12;278(50):50377-85
pubmed: 14522979
Oncogene. 2003 Feb 13;22(6):919-23
pubmed: 12584571
Heredity (Edinb). 2005 Jun;94(6):571-6
pubmed: 15815711
Cancer Res. 2014 Aug 15;74(16):4504-14
pubmed: 24970482
Cell Mol Life Sci. 2020 Dec;77(24):5059-5077
pubmed: 32462405
Front Oncol. 2019 Apr 29;9:331
pubmed: 31110966
Blood. 2010 Mar 18;115(11):2319-28
pubmed: 20075159
Oncogene. 2006 Jun 29;25(28):3939-47
pubmed: 16474844
Adv Exp Med Biol. 2020;1221:3-59
pubmed: 32274705
Br J Cancer. 2016 Oct 11;115(8):909-911
pubmed: 27657336