MicroRNA-135b Promotes Cancer Progression by Acting as a Downstream Effector of Oncogenic Pathways in Colon Cancer

• Published in: Cancer cell Vol. 25; no. 4; pp. 469 - 483
• Main Authors: Valeri, Nicola, Braconi, Chiara, Gasparini, Pierluigi, Murgia, Claudio, Lampis, Andrea, Paulus-Hock, Viola, Hart, Jonathan R., Ueno, Lynn, Grivennikov, Sergei I., Lovat, Francesca, Paone, Alessio, Cascione, Luciano, Sumani, Khlea M., Veronese, Angelo, Fabbri, Muller, Carasi, Stefania, Alder, Hansjuerg, Lanza, Giovanni, Gafa’, Roberta, Moyer, Mary P., Ridgway, Rachel A., Cordero, Julia, Nuovo, Gerard J., Frankel, Wendy L., Rugge, Massimo, Fassan, Matteo, Groden, Joanna, Vogt, Peter K., Karin, Michael, Sansom, Owen J., Croce, Carlo M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14-04-2014; Cell Press
• Subjects: Animals; Cell Growth Processes - genetics; Cell Line, Tumor; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Disease Models, Animal; Disease Progression; Heterografts; Humans; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Transfection
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccr.2014.03.006

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.
•miR-135b is overexpressed in mouse and human colorectal cancer•miR-135b overexpression is associated with poor clinical outcome•miR-135b activation is triggered by oncogenic pathways in colorectal cancer•miR-135b represents a therapeutic target for colorectal cancer
Valeri et al. identify miR-135b as a key oncogenic pathway effector involved in transformation and colorectal cancer (CRC) progression. Upregulation of miR-135b in human CRCs correlates with poor clinical outcome. miR-135b targets several tumor suppressor genes and is a potential target for CRC therapy.