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Cancer Cell. 2014 Apr 14;25(4):469-83. doi: 10.1016/j.ccr.2014.03.006.

MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer.

Author information

1
Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK. Electronic address: nicola.valeri@icr.ac.uk.
2
Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK.
3
Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
4
Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK.
5
Department of Molecular & Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
6
Department of Pharmacology, School of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
7
Aging Research Center, G.d'Annunzio University Foundation, Chieti 66100, Italy.
8
Department of Pathology, University of Ferrara, Ferrara 44121, Italy.
9
INCELL Corporation, San Antonio, TX 78249, USA.
10
Department of Pathology, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA.
11
Department of Pathology, University of Padova, Padova 35121, Italy.
12
Human Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, USA. Electronic address: carlo.croce@osumc.edu.

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.

PMID:
24735923
PMCID:
PMC3995091
DOI:
10.1016/j.ccr.2014.03.006
[Indexed for MEDLINE]
Free PMC Article

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