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SOX2 modulates alternative splicing in transitional cell carcinoma

Chun-Liang Tung1, Pei-Hsuan Hou, Yung-Ling Kao

  • 1Department of Pathology, Chia-Yi Christian Hospital, Chiayi, Taiwan.

Biochemical and Biophysical Research Communications
|February 9, 2010
PubMed

Insights

Aberrant alternative splicing is implicated in cancer. This study reveals sex-determining region Y-box protein 2 (SOX2) acts as a splicing factor, modulating alternative splicing in transitional cell carcinoma (TCC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Aberrant alternative splicing of cellular regulators is linked to cancer development.
  • Transitional cell carcinoma (TCC) is a significant form of cancer where splicing alterations may play a role.

Purpose of the Study:

  • To investigate the influence of altered alternative splicing on TCC development.
  • To identify specific splicing alterations and regulatory factors in TCC.

Main Methods:

  • Splicing activity was examined in TCC cell lines (TSGH8301, BFTC905) and a reference uroepithelial cell line (SV-HUC-1).
  • Gene expression profiling and validation were used to identify upregulated genes.
  • In vivo splicing reporter assays and in vitro pull-down assays were performed.

Main Results:

  • Significant alterations in splice site selection were observed in TCC cell lines.
  • Sex-determining region Y-box protein 2 (SOX2) was found to be specifically upregulated in the BFTC905 TCC cell line.
  • Ectopic SOX2 expression modulated alternative splicing, and SOX2 demonstrated RNA-binding capability, suggesting it functions as a splicing factor.

Conclusions:

  • SOX2 plays a role in modulating alternative splicing in transitional cell carcinoma.
  • SOX2's function as a splicing factor may contribute to TCC development.
  • Targeting SOX2-mediated alternative splicing could be a potential therapeutic strategy for TCC.

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