title: Oncosuppressive role of p53-induced miR-205 in triple negative breast cancer.
abstract: An increasing body of evidence highlights an intriguing interaction between microRNAs and transcriptional factors involved in determining cell fate, including the well known "genome guardian" p53. Here we show that miR-205, oncosuppressive microRNA lost in breast cancer, is directly transactivated by oncosuppressor p53. Moreover, evaluating miR-205 expression in a panel of cell lines belonging to the highly aggressive triple negative breast cancer (TNBC) subtype, which still lacks an effective targeted therapy and characterized by an extremely undifferentiated and mesenchymal phenotype, we demonstrated that this microRNA is critically down-expressed compared to a normal-like cell line. Re-expression of miR-205 where absent strongly reduces cell proliferation, cell cycle progression and clonogenic potential in vitro, and inhibits tumor growth in vivo, and this tumor suppressor activity is at least partially exerted through targeting of E2F1, master regulator of cell cycle progression, and LAMC1, component of extracellular matrix involved in cell adhesion, proliferation and migration.
authors.affiliation: Departments of Molecular Virology, Immunology and Human Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Piovan
authors.forename: Dario
authors.initials: D
authors.lastname: Palmieri
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Di Leva
authors.forename: Luca
authors.initials: L
authors.lastname: Braccioli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Casalini
authors.forename: Gerard
authors.initials: G
authors.lastname: Nuovo
authors.forename: Monica
authors.initials: M
authors.lastname: Tortoreto
authors.forename: Marianna
authors.initials: M
authors.lastname: Sasso
authors.forename: Ilaria
authors.initials: I
authors.lastname: Plantamura
authors.forename: Tiziana
authors.initials: T
authors.lastname: Triulzi
authors.forename: Cristian
authors.initials: C
authors.lastname: Taccioli
authors.forename: Elda
authors.initials: E
authors.lastname: Tagliabue
authors.forename: Marilena V
authors.initials: MV
authors.lastname: Iorio
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D020218:Response Elements / Q000235:genetics; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D050687:E2F1 Transcription Factor; D007797:Laminin; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; C493753:E2F1 protein, human; C534425:MIR205, human; C089141:laminin gamma 1