title: Tumor microenvironment-associated modifications of alternative splicing.
abstract: Pre-mRNA alternative splicing is modified in cancer, but the origin and specificity of these changes remain unclear. Here, we probed ovarian tumors to identify cancer-associated splicing isoforms and define the mechanism by which splicing is modified in cancer cells. Using high-throughput quantitative PCR, we monitored the expression of splice variants in laser-dissected tissues from ovarian tumors. Surprisingly, changes in alternative splicing were not limited to the tumor tissues but were also found in the tumor microenvironment. Changes in the tumor-associated splicing events were found to be regulated by splicing factors that are differentially expressed in cancer tissues. Overall, ∼20% of the alternative splicing events affected by the down-regulation of the splicing factors QKI and RBFOX2 were altered in the microenvironment of ovarian tumors. Together, our results indicate that the tumor microenvironment undergoes specific changes in alternative splicing orchestrated by a limited number of splicing factors.
authors: Jean-Philippe
authors: JP
authors: Brosseau
authors: Jean-François
authors: JF
authors: Lucier
authors: Hanad
authors: H
authors: Nwilati
authors: Philippe
authors: P
authors: Thibault
authors: Daniel
authors: D
authors: Garneau
authors: Daniel
authors: D
authors: Gendron
authors: Mathieu
authors: M
authors: Durand
authors: Sonia
authors: S
authors: Couture
authors: Elvy
authors: E
authors: Lapointe
authors: Panagiotis
authors: P
authors: Prinos
authors: Roscoe
authors: R
authors: Klinck
authors: Jean-Pierre
authors: JP
authors: Perreault
authors: Benoit
authors: B
authors: Chabot
authors: Sherif
authors: S
authors: Abou-Elela
mesh_terms: D017398:Alternative Splicing; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D061346:Laser Capture Microdissection; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D020033:Protein Isoforms; C490832:QKI protein, human; C454924:RBFOX2 protein, human; D022821:RNA Splice Sites; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins
keywords: RNA binding proteins; alternative splicing; laser capture microdissection; ovarian cancer; tumor microenvironment