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Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events

Jung-Chun Lin1, Ching-Yu Lin2, Woan-Yuh Tarn3

  • 1School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, 110, Taipei, Taiwan lin2511@tmu.edu.tw.

RNA (New York, N.Y.)
|August 21, 2014
PubMed

Insights

Altered RNA splicing, driven by SRPK1 and RBM4, promotes breast cancer by reducing apoptosis. This SRPK1-RBM4 network impacts cancer cell survival and tumorigenesis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Splicing

Background:

  • Aberrant pre-messenger RNA splicing is a hallmark of cancer.
  • Serine-arginine protein kinase 1 (SRPK1) is implicated in splicing dysregulation in malignant cells.

Purpose of the Study:

  • To investigate the role of RNA-binding motif protein 4 (RBM4) and SRPK1 in breast cancer splicing.
  • To elucidate the mechanism by which RBM4 and SRPK1 influence breast cancer cell apoptosis.

Main Methods:

  • Correlation analysis of RBM4 and SRPK1 expression in breast cancer cells.
  • Investigating transcript production via RBM4 overexpression and SRPK1 gene silencing.
  • Studying RBM4 binding to specific RNA elements.

Main Results:

  • Cytoplasmic accumulation of RBM4 correlates with SRPK1 upregulation in breast cancer.
  • RBM4 overexpression and SRPK1 gene silencing induce IR-B and MCL-1S transcripts.
  • RBM4 binds to MCL-1 exon2 and downstream intron, promoting exon exclusion.
  • RBM4 upregulates IR-B and MCL-1S, reducing apoptotic resistance in breast cancer cells.

Conclusions:

  • The SRPK1-RBM4 network regulates splicing events in breast cancer.
  • This network contributes to tumorigenesis by altering sensitivity to apoptotic signals.
Keywords:
MCL-1RNA binding motif protein 4alternative splicingbreast cancer

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