MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer.
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Date
2014-04-14Author
Valeri, N
Braconi, C
Gasparini, P
Murgia, C
Lampis, A
Paulus-Hock, V
Hart, JR
Ueno, L
Grivennikov, SI
Lovat, F
Paone, A
Cascione, L
Sumani, KM
Veronese, A
Fabbri, M
Carasi, S
Alder, H
Lanza, G
Gafa', R
Moyer, MP
Ridgway, RA
Cordero, J
Nuovo, GJ
Frankel, WL
Rugge, M
Fassan, M
Groden, J
Vogt, PK
Karin, M
Sansom, OJ
Croce, CM
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Cell Line, Tumor
Animals
Mice, Inbred C57BL
Humans
Mice
Mice, Nude
Colonic Neoplasms
Disease Models, Animal
Disease Progression
MicroRNAs
Immunohistochemistry
Transfection
Cell Growth Processes
Heterografts
Research team
Signal Transduction & Molecular Pharmacology
Evolutionary Genomics & Modelling
Gastrointestinal Cancer Biology and Genomics
Language
eng
Date accepted
2014-03-06
License start date
2014-04
Citation
Cancer cell, 2014, 25 (4), pp. 469 - 483
Publisher
CELL PRESS