Circ_0081143 Contributes to Gastric Cancer Malignant Development and Doxorubicin Resistance by Elevating the Expression of YES1 by Targeting mziR-129-2-3p.
Circ_0081143
Doxorubicin
Stomach neoplasms
YES1
miR-129-2-3p
Journal
Gut and liver
ISSN: 2005-1212
Titre abrégé: Gut Liver
Pays: Korea (South)
ID NLM: 101316452
Informations de publication
Date de publication:
15 11 2022
15 11 2022
Historique:
received:
25
08
2021
revised:
04
11
2021
accepted:
17
11
2021
pubmed:
11
6
2022
medline:
19
11
2022
entrez:
10
6
2022
Statut:
ppublish
Résumé
The increased mortality of gastric cancer (GC) is mainly attributed to the development of chemoresistance. Circular RNAs, as the novel type of biomarkers in GC, have attracted wide attention. The purpose of this study was to investigate the functional role of circ_0081143 in GC with doxorubicin (DR) resistance and its potential action mechanism. The expression of circ_0081143, miR-129-2-3p and YES proto-oncogene 1 (YES1) in GC tissues and cells was measured by quantitative real-time polymerase chain reaction. The half maximal inhibitory concentration value was calculated based on the MTT cell viability assay. Cell proliferation and apoptosis were monitored by MTT and flow cytometry assays. Transwell assays were employed to check cell migration and invasion. The protein levels of YES1 and apoptosis-related proteins were detected by western blotting. The interaction between miR-129-2-3p and circ_0081143 or YES1 was verified by dual-luciferase reporter and pull-down assays. A tumorigenicity assay was conducted to verify the role of circ_0081143 in vivo. Circ_0081143 was highly expressed in DR-resistant GC tumor tissues and cells. Depletion of circ_0081143 reduced DR resistance and inhibited DR-resistant GC cell proliferation, migration and invasion. Circ_0081143 targeted miR-129-2-3p and inhibited the role of miR-129-2-3p. In addition, YES1 was a target of miR-129-2-3p, and its function was suppressed by miR-129-2-3p. Importantly, circ_0081143 positively modulated the expression of YES1 through mediating miR-129-2-3p. Circ_0081143 knockdown weakened the DR-resistant GC tumor growth in vivo. Circ_0081143 knockdown weakened DR resistance and blocked the development of DR-resistant GC by regulating the miR-129-2-3p/YES1 axis. Our data suggest that circ_0081143 is a promising target for the treatment of GC with DR resistance.
Sections du résumé
Background/Aims
The increased mortality of gastric cancer (GC) is mainly attributed to the development of chemoresistance. Circular RNAs, as the novel type of biomarkers in GC, have attracted wide attention. The purpose of this study was to investigate the functional role of circ_0081143 in GC with doxorubicin (DR) resistance and its potential action mechanism.
Methods
The expression of circ_0081143, miR-129-2-3p and YES proto-oncogene 1 (YES1) in GC tissues and cells was measured by quantitative real-time polymerase chain reaction. The half maximal inhibitory concentration value was calculated based on the MTT cell viability assay. Cell proliferation and apoptosis were monitored by MTT and flow cytometry assays. Transwell assays were employed to check cell migration and invasion. The protein levels of YES1 and apoptosis-related proteins were detected by western blotting. The interaction between miR-129-2-3p and circ_0081143 or YES1 was verified by dual-luciferase reporter and pull-down assays. A tumorigenicity assay was conducted to verify the role of circ_0081143 in vivo.
Results
Circ_0081143 was highly expressed in DR-resistant GC tumor tissues and cells. Depletion of circ_0081143 reduced DR resistance and inhibited DR-resistant GC cell proliferation, migration and invasion. Circ_0081143 targeted miR-129-2-3p and inhibited the role of miR-129-2-3p. In addition, YES1 was a target of miR-129-2-3p, and its function was suppressed by miR-129-2-3p. Importantly, circ_0081143 positively modulated the expression of YES1 through mediating miR-129-2-3p. Circ_0081143 knockdown weakened the DR-resistant GC tumor growth in vivo.
Conclusions
Circ_0081143 knockdown weakened DR resistance and blocked the development of DR-resistant GC by regulating the miR-129-2-3p/YES1 axis. Our data suggest that circ_0081143 is a promising target for the treatment of GC with DR resistance.
Identifiants
pubmed: 35686503
pii: gnl210354
doi: 10.5009/gnl210354
pmc: PMC9668504
doi:
Substances chimiques
MicroRNAs
0
RNA, Circular
0
Doxorubicin
80168379AG
YES1 protein, human
EC 2.7.10.2
Proto-Oncogene Proteins c-yes
EC 2.7.10.2
Mirn129 microRNA, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
861-874Références
FEBS J. 2016 Jun;283(12):2326-39
pubmed: 27093644
Med Sci Monit. 2019 Apr 05;25:2488-2504
pubmed: 30948703
Int J Cancer. 2015 Mar 1;136(5):E359-86
pubmed: 25220842
J Cell Biochem. 2020 Jan;121(1):482-488
pubmed: 31310382
Biochem Biophys Res Commun. 2001 Mar 23;282(1):186-93
pubmed: 11263990
Mol Cancer. 2017 Aug 17;16(1):139
pubmed: 28818100
Anticancer Agents Med Chem. 2016;16(3):318-34
pubmed: 26234359
Oncogene. 2018 Feb 1;37(5):555-565
pubmed: 28991235
Eur J Cancer. 2014 May;50(7):1330-44
pubmed: 24650579
J Biotechnol. 2016 Nov 20;238:42-51
pubmed: 27671698
Mol Cell. 2015 Jun 4;58(5):870-85
pubmed: 25921068
Nature. 2013 Mar 21;495(7441):333-8
pubmed: 23446348
Cancer Sci. 2019 Aug;110(8):2549-2557
pubmed: 31162771
J Surg Oncol. 2017 Apr;115(5):603-614
pubmed: 28181265
Gene. 2013 Dec 10;532(1):87-93
pubmed: 24055727
Cancer Cell Int. 2019 Feb 01;19:25
pubmed: 30733646
Oncol Rep. 2016 May;35(5):2963-9
pubmed: 26935022
Med Oncol. 2013 Mar;30(1):365
pubmed: 23307240
Mol Cell. 2014 Oct 2;56(1):55-66
pubmed: 25242144
PeerJ. 2018 Jul 02;6:e5180
pubmed: 30002985
Curr Top Microbiol Immunol. 2017;400:277-304
pubmed: 28124158
Oncogene. 2013 Feb 7;32(6):759-67
pubmed: 22430206
RNA Biol. 2017 May 4;14(5):514-521
pubmed: 26649774
Nat Rev Gastroenterol Hepatol. 2017 Aug;14(8):467-478
pubmed: 28513632
Mol Cancer. 2019 Mar 30;18(1):71
pubmed: 30927924
Cancer Res. 2019 Nov 15;79(22):5734-5745
pubmed: 31391186
CA Cancer J Clin. 2017 Jan;67(1):7-30
pubmed: 28055103
Nat Struct Mol Biol. 2009 Feb;16(2):144-50
pubmed: 19182800