title: miR-221 affects multiple cancer pathways by modulating the level of hundreds messenger RNAs.
abstract: microRNA miR-221 is frequently over-expressed in a variety of human neoplasms. Aim of this study was to identify new miR-221 gene targets to improve our understanding on the molecular tumor-promoting mechanisms affected by miR-221. Gene expression profiling of miR-221-transfected-SNU-398 cells was analyzed by the Sylamer algorithm to verify the enrichment of miR-221 targets among down-modulated genes. This analysis revealed that enforced expression of miR-221 in SNU-398 cells caused the down-regulation of 602 mRNAs carrying sequences homologous to miR-221 seed sequence within their 3'UTRs. Pathways analysis performed on these genes revealed their prominent involvement in cell proliferation and apoptosis. Activation of E2F, MYC, NFkB, and β-catenin pathways was experimentally proven. Some of the new miR-221 target genes, including RB1, WEE1 (cell cycle inhibitors), APAF1 (pro-apoptotic), ANXA1, CTCF (transcriptional repressor), were individually validated as miR-221 targets in SNU-398, HepG2, and HEK293 cell lines. By identifying a large set of miR-221 gene targets, this study improves our knowledge about miR-221 molecular mechanisms involved in tumorigenesis. The modulation of mRNA level of 602 genes confirms the ability of miR-221 to promote cancer by affecting multiple oncogenic pathways.
authors: Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Università di Ferrara Ferrara, Italy.
authors: Laura
authors: L
authors: Lupini
authors: Cristian
authors: C
authors: Bassi
authors: Manuela
authors: M
authors: Ferracin
authors: Nenad
authors: N
authors: Bartonicek
authors: Lucilla
authors: L
authors: D'Abundo
authors: Barbara
authors: B
authors: Zagatti
authors: Elisa
authors: E
authors: Callegari
authors: Gentian
authors: G
authors: Musa
authors: Farzaneh
authors: F
authors: Moshiri
authors: Laura
authors: L
authors: Gramantieri
authors: Fernando J
authors: FJ
authors: Corrales
authors: Anton J
authors: AJ
authors: Enright
authors: Silvia
authors: S
authors: Sabbioni
authors: Massimo
authors: M
authors: Negrini
keywords: Sylamer; gene targets; miR-221; microRNA; microarray
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