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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Role of the splicing factor SRSF4 in cisplatin-induced modifications of pre-mRNA splicing and apoptosis

Authors: Maude Gabriel, Yves Delforge, Adeline Deward, Yvette Habraken, Benoit Hennuy, Jacques Piette, Roscoe Klinck, Benoit Chabot, Alain Colige, Charles Lambert

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Modification of splicing by chemotherapeutic drugs has usually been evaluated on a limited number of pre-mRNAs selected for their recognized or potential importance in cell proliferation or apoptosis. However, the pathways linking splicing alterations to the efficiency of cancer therapy remain unclear.

Methods

Next-generation sequencing was used to analyse the transcriptome of breast carcinoma cells treated by cisplatin. Pharmacological inhibitors, RNA interference, cells deficient in specific signalling pathways, RT-PCR and FACS analysis were used to investigate how the anti-cancer drug cisplatin affected alternative splicing and the cell death pathway.

Results

We identified 717 splicing events affected by cisplatin, including 245 events involving cassette exons. Gene ontology analysis indicates that cell cycle, mRNA processing and pre-mRNA splicing were the main pathways affected. Importantly, the cisplatin–induced splicing alterations required class I PI3Ks P110β but not components such as ATM, ATR and p53 that are involved in the DNA damage response. The siRNA-mediated depletion of the splicing regulator SRSF4, but not SRSF6, expression abrogated many of the splicing alterations as well as cell death induced by cisplatin.

Conclusion

Many of the splicing alterations induced by cisplatin are caused by SRSF4 and they contribute to apoptosis in a process requires class I PI3K.
Appendix
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Metadata
Title
Role of the splicing factor SRSF4 in cisplatin-induced modifications of pre-mRNA splicing and apoptosis
Authors
Maude Gabriel
Yves Delforge
Adeline Deward
Yvette Habraken
Benoit Hennuy
Jacques Piette
Roscoe Klinck
Benoit Chabot
Alain Colige
Charles Lambert
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1259-0

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