title: Cancer-associated regulation of alternative splicing.
abstract: Alternative splicing of pre-mRNA increases the diversity of protein functions. Here we show that about half of all active alternative splicing events in ovarian and breast tissues are changed in tumors, and many seem to be regulated by a single factor; sequence analysis revealed binding sites for the RNA binding protein FOX2 downstream of one-third of the exons skipped in cancer. High-resolution analysis of FOX2 binding sites defined the precise positions relative to alternative exons at which the protein may function as either a silencer or an enhancer. Most of the identified targets were shifted in the same direction by FOX2 depletion in cell lines as they were in breast and ovarian cancer tissues. Notably, we found expression of FOX2 itself is downregulated in ovarian cancer and its splicing is altered in breast cancer samples. These results suggest that the decreased expression of FOX2 in cancer tissues modulates splicing and controls proliferation.
authors.affiliation: Laboratoire de génomique fonctionnelle de l'Université de Sherbrooke, Sherbrooke, Québec, Canada.
authors.forename: Julian P
authors.initials: JP
authors.lastname: Venables
authors.forename: Roscoe
authors.initials: R
authors.lastname: Klinck
authors.forename: ChuShin
authors.initials: C
authors.lastname: Koh
authors.forename: Julien
authors.initials: J
authors.lastname: Gervais-Bird
authors.forename: Anne
authors.initials: A
authors.lastname: Bramard
authors.forename: Lyna
authors.initials: L
authors.lastname: Inkel
authors.forename: Mathieu
authors.initials: M
authors.lastname: Durand
authors.forename: Sonia
authors.initials: S
authors.lastname: Couture
authors.forename: Ulrike
authors.initials: U
authors.lastname: Froehlich
authors.forename: Elvy
authors.initials: E
authors.lastname: Lapointe
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Lucier
authors.forename: Philippe
authors.initials: P
authors.lastname: Thibault
authors.forename: Claudine
authors.initials: C
authors.lastname: Rancourt
authors.forename: Karine
authors.initials: K
authors.lastname: Tremblay
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Prinos
authors.forename: Benoit
authors.initials: B
authors.lastname: Chabot
authors.forename: Sherif Abou
authors.initials: SA
authors.lastname: Elela
mesh_terms: D017398:Alternative Splicing; D020816:Amino Acid Motifs; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005091:Exons; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry; D017422:Sequence Analysis, DNA
chemical_list: D016601:RNA-Binding Proteins