miR-23a-3p is a Key Regulator of IL-17C-Induced Tumor Angiogenesis in Colorectal Cancer.
Animals
Base Sequence
Carcinogenesis
/ genetics
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Colorectal Neoplasms
/ genetics
Disease Progression
Endothelial Cells
/ metabolism
Female
Gene Expression Regulation, Neoplastic
Humans
Interleukin-17
/ metabolism
Intestines
/ blood supply
Mice, Inbred BALB C
Mice, Nude
MicroRNAs
/ genetics
Microvessels
/ pathology
Models, Biological
Neovascularization, Pathologic
/ genetics
STAT3 Transcription Factor
/ metabolism
Semaphorins
/ metabolism
Signal Transduction
Up-Regulation
/ genetics
Vascular Endothelial Growth Factor A
/ biosynthesis
Vascular Endothelial Growth Factor Receptor-2
/ antagonists & inhibitors
angiogenesis
colorectal cancer
interleukin-17C
microRNA
vascular endothelial growth factor
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
01 06 2020
01 06 2020
Historique:
received:
22
04
2020
revised:
17
05
2020
accepted:
26
05
2020
entrez:
5
6
2020
pubmed:
5
6
2020
medline:
6
3
2021
Statut:
epublish
Résumé
MicroRNAs (miRNAs) have emerged as key players in tumor angiogenesis. Interleukin-17C (IL-17C) was identified to promote colorectal cancer (CRC) progression. Therefore, we aimed to investigate the effect of IL-17C on tumor angiogenesis, the involvement of miR-23a-3p in IL-17C signaling, and the direct target gene of miR-23a-3p in CRC. In vitro and ex vivo angiogenesis, a mouse xenograft experiment, and immunostaining were performed to test the effect of IL-17C on tumor angiogenesis. ELISA, quantitative real time PCR, and gene silencing were used to uncover the underlying mechanism. IL-17C induced angiogenesis of intestinal endothelial cells, subsequently enhancing cell invasion and migration of DLD-1 cells. IL-17C-stimulated DLD-1 cells produced vascular endothelial growth factor (VEGF) to enhance angiogenesis. Moreover, IL-17C markedly accelerated xenograft tumor growth, which was manifested by substantially reduced tumor growth when treated with the VEGF receptor 2 inhibitor Ki8751. Accordingly, Ki8751 suppressed the expression of IL-17C-stimulated PECAM and VE-cadherin in xenografts. Furthermore, IL-17C activated STAT3 to increase the expression of miR-23a-3p that suppressed semaphorin 6D (SEMA6D) expression, thereby permitting VEGF production. Taken together, our study demonstrates that IL-17C promotes tumor angiogenesis through VEGF production via a STAT3/miR-23a-3p/SEMA6D axis, suggesting its potential as a novel target for anti-CRC therapy.
Identifiants
pubmed: 32492770
pii: cells9061363
doi: 10.3390/cells9061363
pmc: PMC7348989
pii:
doi:
Substances chimiques
Interleukin-17
0
MIRN23a microRNA, human
0
MicroRNAs
0
SEMA6D protein, human
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Semaphorins
0
Vascular Endothelial Growth Factor A
0
Vascular Endothelial Growth Factor Receptor-2
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
Hum Gene Ther Methods. 2013 Feb;24(1):28-37
pubmed: 23360398
Am J Physiol Gastrointest Liver Physiol. 2009 Nov;297(5):G999-G1008
pubmed: 20501448
Mol Carcinog. 2014 Jan;53(1):67-76
pubmed: 22911886
Eur J Immunol. 2013 Jun;43(6):1518-28
pubmed: 23529839
J Intern Med. 2013 Feb;273(2):114-27
pubmed: 23216836
Oncogenesis. 2013 Sep 16;2:e71
pubmed: 24042735
World J Gastroenterol. 2013 May 28;19(20):2985-96
pubmed: 23716978
CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29
pubmed: 25559415
Cell. 2012 Apr 27;149(3):515-24
pubmed: 22541426
J Immunol. 2005 Nov 1;175(9):6177-89
pubmed: 16237115
J Immunol. 2015 Sep 15;195(6):2591-600
pubmed: 26259585
Oncol Lett. 2016 Aug;12(2):933-943
pubmed: 27446373
Mol Cancer. 2011 Dec 15;10:150
pubmed: 22171994
FEBS Lett. 2015 Jun 22;589(14):1694-701
pubmed: 25957774
Sci Rep. 2015 Nov 03;5:16053
pubmed: 26524953
J Exp Med. 2009 Jul 6;206(7):1457-64
pubmed: 19564351
Crit Rev Oncol Hematol. 2014 Jan;89(1):129-39
pubmed: 24029605
Proc Natl Acad Sci U S A. 2011 May 17;108(20):8287-92
pubmed: 21536891
Biochem Biophys Res Commun. 2011 Apr 8;407(2):348-54
pubmed: 21396350
Exp Cell Res. 2013 May 15;319(9):1306-16
pubmed: 23422037
Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):773-8
pubmed: 10639155
Biochem Biophys Res Commun. 2008 Sep 26;374(3):533-7
pubmed: 18655770
Int J Breast Cancer. 2015;2015:539721
pubmed: 25973277
Mol Aspects Med. 2007 Feb;28(1):59-86
pubmed: 17306360
Vascul Pharmacol. 2006 Apr;44(4):206-14
pubmed: 16481221
Nat Rev Genet. 2009 Jun;10(6):353-8
pubmed: 19434079
J Math Biol. 2015 Feb;70(3):485-532
pubmed: 24615007
Dev Cell. 2011 Aug 16;21(2):301-14
pubmed: 21802375
Clin Hemorheol Microcirc. 2007;37(1-2):57-62
pubmed: 17641395
Am J Physiol Heart Circ Physiol. 2018 Oct 1;315(4):H838-H846
pubmed: 29906231
Vascul Pharmacol. 2011 Oct;55(4):79-86
pubmed: 21777698
Cardiovasc Res. 2017 May 1;113(6):681-691
pubmed: 28453731
Dev Biol. 2014 Jul 15;391(2):241-50
pubmed: 24809797
Genes Dev. 2004 Feb 15;18(4):435-47
pubmed: 14977921
Mol Cancer. 2017 Jul 6;16(1):116
pubmed: 28683746
Nat Immunol. 2011 Oct 12;12(12):1159-66
pubmed: 21993848
Exp Cell Res. 2013 May 15;319(9):1324-30
pubmed: 23262024
Cytokine. 2017 Jan;89:34-44
pubmed: 26883678
Hepatology. 2012 Jul;56(1):186-97
pubmed: 22318941
Nat Immunol. 2011 Oct 12;12(12):1151-8
pubmed: 21993849
Immunity. 2014 Jan 16;40(1):140-52
pubmed: 24412611
Drug Des Devel Ther. 2015 Mar 18;9:1679-89
pubmed: 25834404
Blood. 2006 Nov 1;108(9):3068-71
pubmed: 16849646
J Surg Oncol. 2017 Apr;115(5):619-630
pubmed: 28194798