MicroRNA-301a (miR-301a) is induced in hepatocellular carcinoma (HCC) and down- regulates the expression of interferon regulatory factor-1.
Apoptosis
HCC
Hypoxia
IRF-1
Proliferation
miR-301a
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
02 04 2020
02 04 2020
Historique:
received:
09
12
2019
accepted:
05
01
2020
pubmed:
29
1
2020
medline:
21
10
2020
entrez:
29
1
2020
Statut:
ppublish
Résumé
Hepatocellular carcinoma (HCC) tumors evade death in part by downregulating expression of the tumor suppressor gene Interferon regulatory factor-1 (IRF-1). However, the molecular mechanisms accounting for IRF-1 suppression in HCC have not been well described. In this study, we identified a novel microRNA-301a (miR-301a) binding site in the 3'-untranslated region (3'- UTR) of the human IRF-1 gene and hypothesized a functional role for miR-301a in regulating HCC growth. We show that miR-301a is markedly upregulated in primary HCC tumors and HCC cell lines, while IRF-1 is down-regulated in a post-transcriptional manner. MiR-301a regulates basal and inducible IRF-1 expression in HCC cells with an inverse relationship between miR-301a and IRF-1 expression in HCC cells. Chronic hypoxia induces miR-301a in HCC in vitro and decreases IRF-1 expression. Finally, miR-301a inhibition increases apoptosis and decreases HCC cell proliferation. These findings suggest that targeting of IRF-1 by miR-301a contributes to the molecular basis for IRF-1 downregulation in HCC and provides new insight into the regulation of HCC by miRNAs.
Identifiants
pubmed: 31987500
pii: S0006-291X(20)30088-7
doi: 10.1016/j.bbrc.2020.01.034
pmc: PMC7857543
mid: NIHMS1662409
pii:
doi:
Substances chimiques
Interferon Regulatory Factor-1
0
MIRN301A microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
273-279Subventions
Organisme : NLM NIH HHS
ID : HHSN276201200017C
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK120531
Pays : United States
Organisme : NIH HHS
ID : S10 OD019973
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA113263
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declared no conflict of interest with respect to this manuscript.
Références
Hepatology. 2010 Mar;51(3):881-90
pubmed: 20146264
Cell. 2009 Feb 20;136(4):642-55
pubmed: 19239886
Int J Cancer. 2008 Aug 15;123(4):972-8
pubmed: 18508316
Gene. 2014 Sep 10;548(1):91-100
pubmed: 25014136
J Interferon Cytokine Res. 2003 Sep;23(9):501-11
pubmed: 14565859
J Viral Hepat. 2012 Jul;19(7):473-9
pubmed: 22676359
Ann Surg Oncol. 2013 Jan;20(1):267-76
pubmed: 22805863
Oncoimmunology. 2012 Nov 1;1(8):1376-1386
pubmed: 23243601
J Interferon Cytokine Res. 2003 Nov;23(11):621-30
pubmed: 14651776
Molecules. 2014 May 19;19(5):6393-406
pubmed: 24853455
Cancer Lett. 2012 Jan 28;314(2):213-22
pubmed: 22056812
Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5826-31
pubmed: 22451906
Oncogene. 2004 Feb 5;23(5):1125-35
pubmed: 14762441
Nature. 1996 Aug 29;382(6594):816-8
pubmed: 8752276
Clin Cancer Res. 2008 Jan 15;14(2):419-27
pubmed: 18223217
Mol Biosyst. 2015 Feb;11(2):532-9
pubmed: 25424171
Oncol Rep. 2016 Aug;36(2):633-40
pubmed: 27279136
Nucleic Acids Res. 2013 Mar 1;41(5):2817-31
pubmed: 23335783
Cancer Biol Ther. 2015;16(7):1029-41
pubmed: 26011589
Oncotarget. 2016 Apr 12;7(15):20953-65
pubmed: 26967567
Annu Rev Immunol. 2008;26:535-84
pubmed: 18303999
Int J Cancer. 2007 Mar 1;120(5):1046-54
pubmed: 17149698
Cell Death Differ. 2010 Apr;17(4):699-709
pubmed: 19851330
Oncol Rep. 2017 Feb;37(2):945-952
pubmed: 28035415
J Gastroenterol. 2014 Feb;49(2):173-84
pubmed: 24258409
Biochem Biophys Res Commun. 2007 Oct 26;362(3):582-6
pubmed: 17723228
Oncogene. 2007 Sep 27;26(44):6420-30
pubmed: 17452973
Int J Clin Exp Pathol. 2015 May 01;8(5):5603-8
pubmed: 26191271