title: miR-135b coordinates progression of ErbB2-driven mammary carcinomas through suppression of MID1 and MTCH2.
abstract: In an attempt to reveal deregulated miRNAs associated with the progression of carcinomas developed in BALB-neuT transgenic mice, we found increased expression of miR-135b during malignancy. Relevantly, we observed that miR-135b is up-regulated in basal or normal-like human breast cancers, and it correlates with patient survival and early metastatization. Therefore, we investigated its biological functions by modulating its expression (up- or down-regulation) in mammary tumor cells. Although no effect was observed on proliferation in cell culture and in orthotopically injected mice, miR-135b was able to control cancer cell stemness in a mammosphere assay, anchorage-independent growth in vitro, and lung cancer cell dissemination in mice after tail vein injections. Focusing on the miR-135b molecular mechanism, we observed that miR-135b controls malignancy via its direct targets, midline 1 (MID1) and mitochondrial carrier homolog 2 (MTCH2), as proved by biochemical and functional rescuing/phenocopying experiments. Consistently, an anti-correlation between miR-135b and MID1 or MTCH2 was found in human primary tumor samples. In conclusion, our research led us to the identification of miR-135b and its targets, MID1 and MTCH2, as relevant coordinators of mammary gland tumor progression.
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Arigoni
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Barutello
authors.forename: Federica
authors.initials: F
authors.lastname: Riccardo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ercole
authors.forename: Daniela
authors.initials: D
authors.lastname: Cantarella
authors.forename: Francesca
authors.initials: F
authors.lastname: Orso
authors.forename: Laura
authors.initials: L
authors.lastname: Conti
authors.forename: Stefania
authors.initials: S
authors.lastname: Lanzardo
authors.forename: Daniela
authors.initials: D
authors.lastname: Taverna
authors.forename: Irene
authors.initials: I
authors.lastname: Merighi
authors.forename: Raffaele A
authors.initials: RA
authors.lastname: Calogero
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.forename: Elena
authors.initials: E
authors.lastname: Quaglino
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D018734:Genes, erbB-2; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation / Q000502:physiology
chemical_list: C544965:MIRN135 microRNA, human; D035683:MicroRNAs; C549289:Mirn135 microRNA, mouse; D033681:Mitochondrial Membrane Transport Proteins; C550380:Mtch2 protein, mouse; D009363:Neoplasm Proteins; D011506:Proteins; D012334:RNA, Neoplasm; C109037:Mid1 protein, mouse; D044767:Ubiquitin-Protein Ligases