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

被引：255

作者：

Valeri, Nicola ^{[1
]}

Braconi, Chiara ^{[1
]}

Gasparini, Pierluigi ^{[2
]}

Murgia, Claudio ^{[3
]}

Lampis, Andrea ^{[1
]}

Paulus-Hock, Viola ^{[1
]}

Hart, Jonathan R. ^{[4
]}

Ueno, Lynn ^{[4
]}

Grivennikov, Sergei I. ^{[5
]}

Lovat, Francesca ^{[2
]}

Paone, Alessio ^{[2
]}

Cascione, Luciano ^{[2
]}

Sumani, Khlea M. ^{[2
]}

Veronese, Angelo ^{[6
]}

Fabbri, Muller ^{[2
,11
,12
]}

Carasi, Stefania ^{[2
]}

Alder, Hansjuerg ^{[2
]}

Lanza, Giovanni ^{[7
]}

Gafa', Roberta ^{[7
]}

Moyer, Mary P. ^{[8
]}

Ridgway, Rachel A. ^{[3
]}

Cordero, Julia ^{[3
]}

Nuovo, Gerard J. ^{[2
]}

Frankel, Wendy L. ^{[9
]}

Rugge, Massimo ^{[10
]}

Fassan, Matteo ^{[10
]}

Groden, Joanna ^{[2
]}

Vogt, Peter K. ^{[4
]}

Karin, Michael ^{[5
]}

Sansom, Owen J. ^{[3
]}

Croce, Carlo M. ^{[2
]}

机构：

[1] Univ Glasgow, Inst Canc Sci, Glasgow G61 1BD, Lanark, Scotland

[2] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43212 USA

[3] Canc Res UK Beatson Inst, Glasgow G61 1BD, Lanark, Scotland

[4] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA

[5] Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA

[6] Univ G dAnnunzio, Aging Res Ctr, I-66100 Chieti, Italy

[7] Univ Ferrara, Dept Pathol, I-44121 Ferrara, Italy

[8] INCELL Corp, San Antonio, TX 78249 USA

[9] Ohio State Univ, Ctr Comprehens Canc, Dept Pathol, Columbus, OH 43212 USA

[10] Univ Padua, Dept Pathol, I-35121 Padua, Italy

[11] Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90027 USA

[12] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA

来源：

CANCER CELL | 2014年 / 25卷 / 04期

关键词：

COLORECTAL-CANCER; CELL-LINES; RECTAL-CANCER; APC; EXPRESSION; MUTATIONS; COLITIS; GENE; ACTIVATION; PROTEIN;

D O I：

10.1016/j.ccr.2014.03.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 nniR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment.

引用

页码：469 / 483

页数：15

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