title: miR148b is a major coordinator of breast cancer progression in a relapse-associated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1.
abstract: Breast cancer is often fatal during its metastatic dissemination. To unravel the role of microRNAs (miRs) during malignancy, we analyzed miR expression in 77 primary breast carcinomas and identified 16 relapse-associated miRs that correlate with survival and/or distinguish tumor subtypes in different datasets. Among them, miR-148b, down-regulated in aggressive breast tumors, was found to be a major coordinator of malignancy. In fact, it is able to oppose various steps of tumor progression when overexpressed in cell lines by influencing invasion, survival to anoikis, extravasation, lung metastasis formation, and chemotherapy response. miR-148b controls malignancy by coordinating a novel pathway involving over 130 genes and, in particular, it directly targets players of the integrin signaling, such as ITGA5, ROCK1, PIK3CA/p110α, and NRAS, as well as CSF1, a growth factor for stroma cells. Our findings reveal the importance of the identified 16 miRs for disease outcome predictions and suggest a critical role for miR-148b in the control of breast cancer progression.
authors.affiliation: Molecular Biotechnology Center (MBC), University of Torino, Via Nizza, 52, 10126 Torino, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cimino
authors.forename: Cristiano
authors.initials: C
authors.lastname: De Pittà
authors.forename: Francesca
authors.initials: F
authors.lastname: Orso
authors.forename: Matteo
authors.initials: M
authors.lastname: Zampini
authors.forename: Silvia
authors.initials: S
authors.lastname: Casara
authors.forename: Elisa
authors.initials: E
authors.lastname: Penna
authors.forename: Elena
authors.initials: E
authors.lastname: Quaglino
authors.forename: Marco
authors.initials: M
authors.lastname: Forni
authors.forename: Christian
authors.initials: C
authors.lastname: Damasco
authors.forename: Eva
authors.initials: E
authors.lastname: Pinatel
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ponzone
authors.forename: Chiara
authors.initials: C
authors.lastname: Romualdi
authors.forename: Cathrin
authors.initials: C
authors.lastname: Brisken
authors.forename: Michele
authors.initials: M
authors.lastname: De Bortoli
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Biglia
authors.forename: Paolo
authors.initials: P
authors.lastname: Provero
authors.forename: Gerolamo
authors.initials: G
authors.lastname: Lanfranchi
authors.forename: Daniela
authors.initials: D
authors.lastname: Taverna
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D018450:Disease Progression; D005260:Female; D006801:Humans; D039482:Integrin alpha5 / Q000096:biosynthesis* / Q000235:genetics; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D039482:Integrin alpha5; D035683:MicroRNAs; D012334:RNA, Neoplasm; D016173:Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D015689:Oncogene Protein p21(ras)