title: MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer.
abstract: MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment.
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK. Electronic address: nicola.valeri@icr.ac.uk.
authors.forename: Nicola
authors.initials: N
authors.lastname: Valeri
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK.
authors.forename: Chiara
authors.initials: C
authors.lastname: Braconi
authors.affiliation: Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gasparini
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK.
authors.forename: Claudio
authors.initials: C
authors.lastname: Murgia
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lampis
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK.
authors.forename: Viola
authors.initials: V
authors.lastname: Paulus-Hock
authors.affiliation: Department of Molecular & Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Hart
authors.affiliation: Department of Molecular & Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Lynn
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authors.lastname: Ueno
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Grivennikov
authors.affiliation: Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lovat
authors.affiliation: Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
authors.forename: Alessio
authors.initials: A
authors.lastname: Paone
authors.affiliation: Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
authors.forename: Luciano
authors.initials: L
authors.lastname: Cascione
authors.affiliation: Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
authors.forename: Khlea M
authors.initials: KM
authors.lastname: Sumani
authors.affiliation: Aging Research Center, G.d'Annunzio University Foundation, Chieti 66100, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Veronese
authors.affiliation: Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
authors.forename: Muller
authors.initials: M
authors.lastname: Fabbri
authors.affiliation: Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
authors.forename: Stefania
authors.initials: S
authors.lastname: Carasi
authors.affiliation: Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
authors.forename: Hansjuerg
authors.initials: H
authors.lastname: Alder
authors.affiliation: Department of Pathology, University of Ferrara, Ferrara 44121, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lanza
authors.affiliation: Department of Pathology, University of Ferrara, Ferrara 44121, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Gafa'
authors.affiliation: INCELL Corporation, San Antonio, TX 78249, USA.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Moyer
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Ridgway
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Cordero
authors.affiliation: Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
authors.affiliation: Department of Pathology, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Frankel
authors.affiliation: Department of Pathology, University of Padova, Padova 35121, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.affiliation: Department of Pathology, University of Padova, Padova 35121, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Groden
authors.affiliation: Department of Molecular & Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Vogt
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK.
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Sansom
authors.affiliation: Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA. Electronic address: carlo.croce@osumc.edu.
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: C544965:MIRN135 microRNA, human; D035683:MicroRNAs
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