Splicing factor proline- and glutamine-rich (SFPQ) protein regulates platinum response in ovarian cancer-modulating SRSF2 activity.
Animals
Antineoplastic Agents, Alkylating
/ pharmacology
Apoptosis
Caspase 8
/ metabolism
Caspase 9
/ genetics
Caspase Inhibitors
/ pharmacology
Cell Line, Tumor
Cisplatin
/ pharmacology
DNA-Binding Proteins
/ antagonists & inhibitors
Drug Resistance, Neoplasm
/ drug effects
Female
Gene Knockdown Techniques
Humans
Mice
Neoplasm Proteins
/ physiology
Ovarian Neoplasms
/ drug therapy
PTB-Associated Splicing Factor
/ physiology
RNA Splicing
RNA, Messenger
/ metabolism
RNA, Neoplasm
/ metabolism
RNA-Binding Proteins
/ antagonists & inhibitors
Recurrence
Serine-Arginine Splicing Factors
/ physiology
Spliceosomes
/ metabolism
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
27
09
2019
accepted:
31
03
2020
revised:
23
03
2020
pubmed:
26
4
2020
medline:
1
12
2020
entrez:
26
4
2020
Statut:
ppublish
Résumé
In epithelial ovarian cancer (EOC), response to platinum (PT)-based chemotherapy dictates subsequent treatments and predicts patients' prognosis. Alternative splicing is often deregulated in human cancers and can be altered by chemotherapy. Whether and how changes in alternative splicing regulation could impact on the response of EOC to PT-based chemotherapy is still not clarified. We identified the splicing factor proline and glutamine rich (SFPQ) as a critical mediator of response to PT in an unbiased functional genomic screening in EOC cells and, using a large cohort of primary and recurrent EOC samples, we observed that it is frequently overexpressed in recurrent PT-treated samples and that its overexpression correlates with PT resistance. At mechanistic level, we show that, under PT treatment, SFPQ, in complex with p54
Identifiants
pubmed: 32332923
doi: 10.1038/s41388-020-1292-6
pii: 10.1038/s41388-020-1292-6
pmc: PMC7253352
doi:
Substances chimiques
Antineoplastic Agents, Alkylating
0
Caspase Inhibitors
0
DNA-Binding Proteins
0
NONO protein, human
0
Neoplasm Proteins
0
PTB-Associated Splicing Factor
0
RNA, Messenger
0
RNA, Neoplasm
0
RNA-Binding Proteins
0
SRSF2 protein, human
147153-65-9
Serine-Arginine Splicing Factors
170974-22-8
CASP8 protein, human
EC 3.4.22.-
Caspase 8
EC 3.4.22.-
Caspase 9
EC 3.4.22.-
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4390-4403Références
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