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

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• 作者：Nicola Valeri¹ ; ¹¹ ; ^{nicola.valeri@icr.ac.uk" class="auth_mail} ; Chiara Braconi¹ ; ¹¹ ; Pierluigi Gasparini² ; Claudio Murgia³ ; Andrea Lampis¹ ; ¹¹ ; Viola Paulus-Hock¹ ; Jonathan R. Hart⁴ ; Lynn Ueno⁴ ; Sergei I. Grivennikov⁵ ; Francesca Lovat² ; Alessio Paone² ; Luciano Cascione² ; ¹² ; Khlea M. Sumani² ; Angelo Veronese⁶ ; Muller Fabbri² ; ¹³ ; ¹⁴ ; Stefania Carasi² ; Hansjuerg Alder² ; Giovanni Lanza⁷ ; Roberta Gafa&rsquo ; ⁷ ; Mary P. Moyer⁸ ; Rachel A. Ridgway³ ; Julia Cordero³ ; Gerard J. Nuovo² ; Wendy L. Frankel⁹ ; Massimo Rugge¹⁰ ; Matteo Fassan¹⁰ ; Joanna Groden² ; Peter K. Vogt⁴ ; Michael Karin⁵ ; Owen J. Sansom³ ; Carlo M. Croce² ; ^{carlo.croce@osumc.edu" class="auth_mail}
• 刊名：Cancer Cell
• 出版年：14 April, 2014
• 年：2014
• 卷：25
• 期：4
• 页码：469-483
• 全文大小：5475 K

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Summary

MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it聽represents a bystander event or actually drives tumor progression in聽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.