Aberrant expression of CPSF1 promotes head and neck squamous cell carcinoma via regulating alternative splicing.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
11
01
2020
accepted:
03
05
2020
entrez:
22
5
2020
pubmed:
22
5
2020
medline:
13
8
2020
Statut:
epublish
Résumé
Alternative mRNA splicing increases protein diversity, and alternative splicing events (ASEs) drive oncogenesis in multiple tumor types. However, the driving alterations that underlie the broad dysregulation of ASEs are incompletely defined. Using head and neck squamous cell carcinoma (HNSCC) as a model, we hypothesized that the genomic alteration of genes associated with the spliceosome may broadly induce ASEs across a broad range of target genes, driving an oncogenic phenotype. We identified 319 spliceosome genes and employed a discovery pipeline to identify 13 candidate spliceosome genes altered in HNSCC using The Cancer Genome Atlas (TCGA) HNSCC data. Phenotypic screens identified amplified and overexpressed CPSF1 as a target gene alteration that was validated in proliferation, colony formation, and apoptosis assays in cell line and xenograft systems as well as in primary HNSCC. We employed knockdown and overexpression assays followed by identification of ASEs regulated by CPSF1 overexpression to identify changes in ASEs, and the expression of these ASEs was validated using RNA from cell line models. Alterations in expression of spliceosome genes, including CPSF1, may contribute to HNSCC by mediating aberrant ASE expression.
Identifiants
pubmed: 32437477
doi: 10.1371/journal.pone.0233380
pii: PONE-D-20-00974
pmc: PMC7241804
doi:
Substances chimiques
Biomarkers, Tumor
0
Cleavage And Polyadenylation Specificity Factor
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
e0233380Subventions
Organisme : NCI NIH HHS
ID : R01 CA177669
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001442
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE023347
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Nucleic Acids Res. 2011 Oct;39(18):e123
pubmed: 21745820
Cell. 2010 Aug 20;142(4):625-36
pubmed: 20705336
Nature. 2015 Jan 29;517(7536):576-82
pubmed: 25631445
Mol Cell Biol. 1996 Oct;16(10):5518-26
pubmed: 8816464
Clin Cancer Res. 2018 Oct 15;24(20):5123-5132
pubmed: 29945995
Cancer Res. 2017 Oct 1;77(19):5248-5258
pubmed: 28733453
J Clin Med. 2017 Jan 18;6(1):
pubmed: 28106769
Nucleic Acids Res. 2013 Oct;41(18):8665-79
pubmed: 23863836
Nat Rev Genet. 2009 Jan;10(1):57-63
pubmed: 19015660
Cancer Lett. 2013 Nov 1;340(2):179-91
pubmed: 23196057
Cancer Res. 2017 Oct 1;77(19):5228-5235
pubmed: 28928128
Oncotarget. 2014 Oct 15;5(19):8906-23
pubmed: 25275298
BMC Genomics. 2006 Dec 27;7:325
pubmed: 17192196
Genes Dev. 1995 Nov 1;9(21):2672-83
pubmed: 7590244
Cancer Res. 2008 Feb 1;68(3):657-63
pubmed: 18245464
Oral Oncol. 1997 Sep;33(5):302-12
pubmed: 9415327
Oral Oncol. 2009 Apr-May;45(4-5):309-16
pubmed: 18804401
Cell. 1993 Aug 27;74(4):597-608
pubmed: 8358789
Nat Struct Mol Biol. 2007 Mar;14(3):185-93
pubmed: 17310252
Sci Rep. 2017 Jun 20;7(1):3896
pubmed: 28634396
Nature. 2008 Nov 27;456(7221):470-6
pubmed: 18978772
Mol Cell. 2005 Dec 22;20(6):881-90
pubmed: 16364913
J Natl Cancer Inst. 2000 May 3;92(9):709-20
pubmed: 10793107
Nature. 2009 Nov 5;462(7269):108-12
pubmed: 19847166
PLoS One. 2014 Mar 27;9(3):e91263
pubmed: 24675808
BMC Bioinformatics. 2013 Jan 16;14:7
pubmed: 23323831
PLoS One. 2014 Jan 16;9(1):e78644
pubmed: 24454679
Histol Histopathol. 2005 Apr;20(2):645-63
pubmed: 15736067
BMC Cancer. 2013 Apr 15;13:192
pubmed: 23587173
Nat Struct Mol Biol. 2009 Jun;16(6):670-6
pubmed: 19448617