Interferon regulatory factor 1(IRF-1) activates anti-tumor immunity via CXCL10/CXCR3 axis in hepatocellular carcinoma (HCC).
Chemokine
Chemokine receptor
Hepatocellular carcinoma
IRF-1
Tumor microenvironment
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
28 05 2021
28 05 2021
Historique:
received:
19
10
2020
revised:
25
02
2021
accepted:
01
03
2021
pubmed:
11
3
2021
medline:
16
9
2021
entrez:
10
3
2021
Statut:
ppublish
Résumé
Interferon regulatory factor 1 (IRF-1) is a tumor suppressor gene in cancer biology with anti-proliferative and pro-apoptotic effect on cancer cells, however mechanisms of IRF-1 regulating tumor microenvironment (TME) in hepatocellular carcinoma (HCC) remain only partially characterized. Here, we investigated that IRF-1 regulates C-X-C motif chemokine 10 (CXCL10) and chemokine receptor 3 (CXCR3) to activate anti-tumor immunity in HCC. We found that IRF-1 mRNA expression was positively correlated with CXCL10 and CXCR3 through qRT-PCR assay in HCC tumors and in analysis of the TCGA database. IRF-1 response elements were identified in the CXCL10 promoter region, and ChIP-qPCR confirmed IRF-1 binding to promote CXCL10 transcription. IRF-2 is a competitive antagonist for IRF-1 mediated transcriptional effects, and overexpression of IRF-2 decreased basal and IFN-γ induced CXCL10 expression. Although IRF-1 upregulated CXCR3 expression in HCC cells, it inhibited proliferation and exerted pro-apoptotic effects, which overcome proliferation partly mediated by activating the CXCL10/CXCR3 autocrine axis. In vitro and in vivo studies showed that IRF-1 increased CD8
Identifiants
pubmed: 33689775
pii: S0304-3835(21)00106-3
doi: 10.1016/j.canlet.2021.03.002
pmc: PMC8009854
mid: NIHMS1683054
pii:
doi:
Substances chimiques
CXCL10 protein, human
0
CXCR3 protein, human
0
Chemokine CXCL10
0
IRF1 protein, human
0
Interferon Regulatory Factor-1
0
Receptors, CXCR3
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
95-106Subventions
Organisme : NICHD NIH HHS
ID : HHSN275201700005C
Pays : United States
Organisme : NLM NIH HHS
ID : HHSN276201200017C
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK120531
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.
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