Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events
- 1School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, 110, Taipei, Taiwan
- 2Institute of Biomedical Sciences, Academia Sinica, 115, Taipei, Taiwan
- Corresponding author: lin2511{at}tmu.edu.tw
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↵3 These authors contributed equally to this work.
Abstract
Imbalanced splicing of premessenger RNA is typical of tumorous malignancies, and the regulatory mechanisms involved in several tumorigenesis-associated splicing events are identified. Elevated expression of serine-arginine protein kinase 1 (SRPK1) may participate in the pathway responsible for the dysregulation of splicing events in malignant tumor cells. In this study, we observed a correlation between the cytoplasmic accumulation of RNA-binding motif protein 4 (RBM4) and up-regulated SRPK1 in breast cancer cells. The production of the IR-B and MCL-1S transcripts was induced separately by the overexpression of RBM4 and SRPK1 gene silencing. Overexpressed RBM4 simultaneously bound to the CU-rich elements within the MCL-1 exon2 and the downstream intron, which subsequently facilitated the exclusion of the regulated exon. Breast cancer cells are deprived of apoptotic resistance through the RBM4-mediated up-regulation of the IR-B and MCL-1S transcripts. These findings suggest that the splicing events regulated by the SRPK1-RMB4 network may contribute to tumorigenesis through altered sensitivity to apoptotic signals in breast cancer cells.
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Footnotes
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.045583.114.
- Received March 31, 2014.
- Accepted June 22, 2014.
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