Department of Pathology, Chia-Yi Christian Hospital, Chiayi, Taiwan.
Biochem Biophys Res Commun. 2010 Mar 12;393(3):420-5. doi: 10.1016/j.bbrc.2010.02.010. Epub 2010 Feb 6.
Aberrant alternative splicing of key cellular regulators may play a pivotal role in cancer development. To investigate the potential influence of altered alternative splicing on the development of transitional cell carcinoma (TCC), splicing activity in the TCC cell lines TSGH8301 and BFTC905 was examined using the SV40-immortalized uroepithelial cell line SV-HUC-1 as a reference. Our results indicate a significant alteration in splice site selection in the TCC cell lines. By gene expression profiling and subsequent validation, we discovered that sex-determining region Y-box protein 2 (SOX2) is specifically upregulated in BFTC905. Furthermore, ectopic expression of SOX2 modulates alternative splicing of the splicing reporter in vivo. More significantly, using an in vitro pull-down assay, it was found that SOX2 exhibits RNA-binding capability. Our observations suggest that SOX2 modulates alternative splicing by functioning as a splicing factor.
关键细胞调节因子的异常剪接可能在癌症发展中发挥关键作用。为了研究改变的选择性剪接对移行细胞癌 (TCC) 发展的潜在影响，使用 SV40 永生化尿路上皮细胞系 SV-HUC-1 作为参照，检查了 TCC 细胞系 TSGH8301 和 BFTC905 中的剪接活性。我们的结果表明 TCC 细胞系中剪接位点选择发生了显著改变。通过基因表达谱分析和随后的验证，我们发现性别决定区 Y 框蛋白 2 (SOX2) 在 BFTC905 中特异性地上调。此外，SOX2 的异位表达可调节体内剪接报告基因的选择性剪接。更重要的是，通过体外拉下测定发现 SOX2 具有 RNA 结合能力。我们的观察表明，SOX2 通过作为剪接因子发挥作用来调节选择性剪接。
