Journal
BMC CANCER
Volume 15, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12885-015-1259-0
Keywords
Cancer therapy; Alternative splicing; PI3K; Apoptosis; Drug efficiency; Cisplatin; SRSF4
Categories
Funding
- National Fund for Scientific Research, Belgium (F.N.R.S-Televie) [7.4634.10]
- Belspo
- Research Concerted Action [ARC 10/15-02]
- Fonds Leon Fredericq of the University of Liege, Belgium
- Canadian Institutes of Health Research [MOP136948]
Ask authors/readers for more resources
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 P110 beta 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available