Downregulation of ubiquitin-specific protease 2 possesses prognostic and diagnostic value and promotes the clear cell renal cell carcinoma progression.
Ubiquitin-specific protease 2 (USP2)
biomarker
clear cell renal cell carcinoma (ccRCC)
deubiquitination
prognosis
targeted therapy
Journal
Annals of translational medicine
ISSN: 2305-5839
Titre abrégé: Ann Transl Med
Pays: China
ID NLM: 101617978
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
entrez:
2
5
2020
pubmed:
2
5
2020
medline:
2
5
2020
Statut:
ppublish
Résumé
Clear cell renal cell carcinoma (ccRCC), characterized by high mortality, invasion, metastasis, recurrence and drug resistance, is the most common malignant tumor of the urinary system. A clear understanding of the underlying molecular mechanisms and its role during tumorigenesis of RCC can contribute to development of prognostic and targeted therapies. We analyzed datasets from the public database, TCGA, Oncomine, for differential expression of ubiquitin-specific protease 2 (USP2), and further investigated its relationship with the clinical stage, pathological grade and prognosis of renal cancer. We used real-time quantitative PCR and western blot analysis to validate USP2 expression in clinical samples and renal cancer cell lines. Finally, we used CCK-8 and transwell assays to determine its effects on biological functions in cells. We observed significantly lower levels of USP2 mRNA in renal cancer, relative to normal, tissues across the four datasets from the Oncomine database (P<0.001), 533 cases from TCGA database (P<0.0001) and 30 pairs of clinical samples (P<0.0001). Similarly, a decreased USP2 protein expression in ccRCC was detected following immunohistochemical (IHC) and western blot analyses. Furthermore, the aberrant expression of USP2 resulted in significant relationship with clinical stage, pathological grade and lower USP2 mRNA expression was interrelated to poor prognosis of renal cell carcinoma. USP2 acted as an independent factor for ccRCC diagnosis, with an AUC of 0.8888 (95% CI: 0.8529 to 0.9246; P<0.0001). Exogenous restoration of USP2 in ccRCC cells resulted in repression of cell proliferation, migration, and invasion. Overall, these results show that USP2 acts as an anti-oncogene and an independent factor for ccRCC prognosis. Positive modulation of USP2 might lead to development of a novel strategy for ccRCC treatment.
Sections du résumé
BACKGROUND
BACKGROUND
Clear cell renal cell carcinoma (ccRCC), characterized by high mortality, invasion, metastasis, recurrence and drug resistance, is the most common malignant tumor of the urinary system. A clear understanding of the underlying molecular mechanisms and its role during tumorigenesis of RCC can contribute to development of prognostic and targeted therapies.
METHODS
METHODS
We analyzed datasets from the public database, TCGA, Oncomine, for differential expression of ubiquitin-specific protease 2 (USP2), and further investigated its relationship with the clinical stage, pathological grade and prognosis of renal cancer. We used real-time quantitative PCR and western blot analysis to validate USP2 expression in clinical samples and renal cancer cell lines. Finally, we used CCK-8 and transwell assays to determine its effects on biological functions in cells.
RESULTS
RESULTS
We observed significantly lower levels of USP2 mRNA in renal cancer, relative to normal, tissues across the four datasets from the Oncomine database (P<0.001), 533 cases from TCGA database (P<0.0001) and 30 pairs of clinical samples (P<0.0001). Similarly, a decreased USP2 protein expression in ccRCC was detected following immunohistochemical (IHC) and western blot analyses. Furthermore, the aberrant expression of USP2 resulted in significant relationship with clinical stage, pathological grade and lower USP2 mRNA expression was interrelated to poor prognosis of renal cell carcinoma. USP2 acted as an independent factor for ccRCC diagnosis, with an AUC of 0.8888 (95% CI: 0.8529 to 0.9246; P<0.0001). Exogenous restoration of USP2 in ccRCC cells resulted in repression of cell proliferation, migration, and invasion.
CONCLUSIONS
CONCLUSIONS
Overall, these results show that USP2 acts as an anti-oncogene and an independent factor for ccRCC prognosis. Positive modulation of USP2 might lead to development of a novel strategy for ccRCC treatment.
Identifiants
pubmed: 32355763
doi: 10.21037/atm.2020.02.141
pii: atm-08-06-319
pmc: PMC7186618
doi:
Types de publication
Journal Article
Langues
eng
Pagination
319Informations de copyright
2020 Annals of Translational Medicine. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: The authors have no conflicts of interest to declare.
Références
Mol Cell Biol. 2000 Sep;20(17):6568-78
pubmed: 10938131
Science. 1996 Nov 1;274(5288):782-4
pubmed: 8864118
Cell. 2009 Jul 23;138(2):389-403
pubmed: 19615732
Biochim Biophys Acta. 2012 Aug;1823(8):1353-65
pubmed: 22659130
J Biol Chem. 2011 Nov 11;286(45):38960-8
pubmed: 21890637
Eur Urol. 2016 Jul;70(1):93-105
pubmed: 26935559
Science. 1996 Nov 1;274(5288):787-9
pubmed: 8864120
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Int J Biol Sci. 2017 Nov 2;13(12):1489-1496
pubmed: 29230097
World J Urol. 2018 Dec;36(12):1927-1942
pubmed: 29948048
Eur J Med Chem. 2018 Apr 25;150:261-267
pubmed: 29529503
Structure. 2006 Aug;14(8):1293-302
pubmed: 16905103
Biol Open. 2012 Aug 15;1(8):789-801
pubmed: 23213472
Cancer Metastasis Rev. 2016 Dec;35(4):589-600
pubmed: 27844253
Oncogene. 2010 Jan 21;29(3):432-41
pubmed: 19838211
Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):8705-10
pubmed: 27436899
BMC Biochem. 2008 Oct 21;9 Suppl 1:S3
pubmed: 19007433
Oncogene. 2013 Mar 28;32(13):1660-9
pubmed: 22710717
Mediators Inflamm. 2017;2017:6909415
pubmed: 29138532
Lancet. 2009 Mar 28;373(9669):1119-32
pubmed: 19269025
Cancer Cell. 2004 Mar;5(3):253-61
pubmed: 15050917
Recent Pat Anticancer Drug Discov. 2009 Jun;4(2):146-56
pubmed: 19519537
PLoS One. 2011;6(9):e25382
pubmed: 21966515
CA Cancer J Clin. 2018 Jan;68(1):7-30
pubmed: 29313949
Clin Cancer Res. 2015 Jan 1;21(1):10-7
pubmed: 25564569
J Biol Chem. 2016 Nov 18;291(47):24628-24640
pubmed: 27681596
J Mol Cell Biol. 2013 Feb;5(1):39-47
pubmed: 22611252
Nature. 1989 Dec 7;342(6250):705-8
pubmed: 2531845
Nat Rev Clin Oncol. 2019 Oct;16(10):621-633
pubmed: 30992569
Semin Cancer Biol. 2019 Apr;55:8-15
pubmed: 30055950
Int Rev Immunol. 2008;27(5):293-319
pubmed: 18853341
Cell Commun Signal. 2014 Jul 16;12:41
pubmed: 25027767
Cell Death Differ. 2012 May;19(5):891-9
pubmed: 22179575
Circ Res. 2016 Feb 5;118(3):410-9
pubmed: 26666640
EMBO J. 2007 Feb 21;26(4):976-86
pubmed: 17290220
BMC Urol. 2015 Aug 07;15:80
pubmed: 26250800
Future Oncol. 2007 Apr;3(2):191-9
pubmed: 17381419
Cell Death Dis. 2019 Mar 28;10(4):285
pubmed: 30918246
Int J Cancer. 2011 Aug 1;129(3):607-18
pubmed: 21480224
Oncogene. 2017 Oct 5;36(40):5631-5638
pubmed: 28581522
Nature. 2013 Jul 4;499(7456):43-9
pubmed: 23792563
J Clin Neurosci. 2013 May;20(5):717-20
pubmed: 23416128
Carcinogenesis. 2014 Jul;35(7):1500-9
pubmed: 24445145
Annu Rev Pathol. 2007;2:145-73
pubmed: 18039096
J Biol Rhythms. 2014 Aug;29(4):243-56
pubmed: 25238854
Eur Urol. 2010 Jul;58(1):75-83
pubmed: 20359812
Eur Urol. 2011 Oct;60(4):644-61
pubmed: 21741163
Am J Physiol Renal Physiol. 2013 Jul 1;305(1):F21-30
pubmed: 23552861
PLoS One. 2016 Jan 12;11(1):e0145155
pubmed: 26756164