生物
RNA剪接
选择性拼接
间充质干细胞
外显子
细胞生物学
上皮-间质转换
癌症研究
基因
遗传学
核糖核酸
下调和上调
作者
Julian P. Venables,Jean-Philippe Brosseau,Gilles Gadéa,Roscoe Klinck,Panagiotis Prinos,Jean‐François Beaulieu,Elvy Lapointe,Mathieu Durand,Philippe Thibault,Karine Tremblay,François Rousset,Jamal Tazi,Sherif Abou Elela,Benoît Chabot
摘要
Alternative splicing provides a critical and flexible layer of regulation intervening in many biological processes to regulate the diversity of proteins and impact cell phenotype. To identify alternative splicing differences that distinguish epithelial from mesenchymal tissues, we have investigated hundreds of cassette exons using a high-throughput reverse transcription-PCR (RT-PCR) platform. Extensive changes in splicing were noted between epithelial and mesenchymal tissues in both human colon and ovarian tissues, with many changes from mostly one splice variant to predominantly the other. Remarkably, many of the splicing differences that distinguish normal mesenchymal from normal epithelial tissues matched those that differentiate normal ovarian tissues from ovarian cancer. Furthermore, because splicing profiling could classify cancer cell lines according to their epithelial/mesenchymal characteristics, we used these cancer cell lines to identify regulators for these specific splicing signatures. By knocking down 78 potential splicing factors in five cell lines, we provide an extensive view of the complex regulatory landscape associated with the epithelial and mesenchymal states, thus revealing that RBFOX2 is an important driver of mesenchymal tissue-specific splicing.
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