Oncogenic splicing factor SRSF3 regulates ILF3 alternative splicing to promote cancer cell proliferation and

Rong Jia1,2, Masahiko Ajiro1, Lulu Yu1

  • 1Tumor Virus RNA Biology Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA.

RNA (New York, N.Y.)
|February 24, 2019
PubMed

Insights

SRSF3 protein controls alternative splicing of interleukin enhancer binding factor 3 (ILF3) in cancer. Aberrant ILF3 forms can suppress or promote tumor growth, impacting cell proliferation and apoptosis.

Area of Science:

  • Molecular Oncology
  • RNA Biology
  • Cancer Research

Background:

  • Alternative RNA splicing is crucial in cancer development.
  • Interleukin enhancer binding factor 3 (ILF3) is a double-strand RNA-binding protein involved in cellular processes.

Purpose of the Study:

  • To investigate the role of SRSF3 in regulating alternative splicing of ILF3.
  • To understand how ILF3 isoforms affect cancer cell proliferation and transformation.

Main Methods:

  • Analysis of SRSF3 and ILF3 coexpression in various cancer types.
  • Investigating the mechanism of SRSF3-mediated ILF3 alternative splicing.
  • Assessing the impact of different ILF3 isoforms on tumor cell behavior.

Main Results:

  • SRSF3 regulates ILF3 alternative splicing, affecting exon 18 inclusion/exclusion and 3' splice site selection.
  • Increased SRSF3 expression in cancer maintains ILF3 isoforms that promote proliferation.
  • Aberrant ILF3 isoforms (isoform-5 and -7) produced upon reduced SRSF3 expression suppress proliferation and induce apoptosis.

Conclusions:

  • SRSF3 plays a critical role in maintaining oncogenic ILF3 isoforms in cancer cells.
  • ILF3 isoforms exhibit dual roles in cancer, with some promoting proliferation and others suppressing it.
  • Targeting SRSF3-mediated ILF3 splicing represents a potential therapeutic strategy in oncology.

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