SOX2 modulates alternative splicing in transitional cell carcinoma.
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.
Tung
Chun-Liang
CL
Department of Pathology, Chia-Yi Christian Hospital, Chiayi, Taiwan.
Hou
Pei-Hsuan
PH
Kao
Yung-Ling
YL
Huang
Yu-Wen
YW
Shen
Chiung-Chun
CC
Cheng
Yi-Hsin
YH
Wu
Shu-Fen
SF
Lee
Moon-Sing
MS
Li
Chin
C
D017500:Adenovirus E1A Proteins / Q000235:genetics; D017398:Alternative Splicing; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; D022821:RNA Splice Sites; D012333:RNA, Messenger; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors