The miR-17-92 MicroRNA Cluster Regulates Multiple Components of the TGF-β Pathway in Neuroblastoma

被引：308

作者：

Mestdagh, Pieter ^{[1
]}

Bostroem, Anna-Karin ^{[2
]}

Impens, Francis ^{[3
,4
]}

Fredlund, Erik ^{[1
,5
,6
]}

Van Peer, Gert ^{[1
]}

De Antonellis, Pasqualino ^{[7
]}

von Stedingk, Kristoffer ^{[2
]}

Ghesquiere, Bart ^{[3
,4
]}

Schulte, Stefanie ^{[8
]}

Dews, Michael ^{[9
,10
]}

Thomas-Tikhonenko, Andrei ^{[9
,10
]}

Schulte, Johannes H. ^{[8
]}

Zollo, Massimo ^{[7
,11
]}

Schramm, Alexander ^{[8
]}

Gevaert, Kris ^{[3
,4
]}

Axelson, Hakan ^{[2
]}

Speleman, Frank ^{[1
]}

Vandesompele, Jo ^{[1
]}

机构：

[1] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium

[2] Lund Univ, Dept Lab Med, Ctr Mol Pathol, SE-20502 Malmo, Sweden

[3] Univ Ghent VIB, Dept Med Prot Res, B-9000 Ghent, Belgium

[4] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium

[5] Lund Univ, Dept Oncol, SE-20502 Malmo, Sweden

[6] Lund Univ, CREATE Hlth, Ctr Translat Canc Res, SE-20502 Malmo, Sweden

[7] Ctr Ingn Genet & Biotecnol Avanzate CEINGE, I-80131 Naples, Italy

[8] Univ Hosp Essen, D-45147 Essen, Germany

[9] Childrens Hosp Philadelphia, Res Inst, Dept Pathol & Lab Med, Div Canc Pathobiol, Philadelphia, PA 19104 USA

[10] Univ Penn, Sch Med, Philadelphia, PA 19104 USA

[11] Univ Naples Federico II, DBBM, I-80131 Naples, Italy

来源：

MOLECULAR CELL | 2010年 / 40卷 / 05期

关键词：

NEURONAL DIFFERENTIATION; MALIGNANT PHENOTYPE; EXPRESSION; BIOGENESIS; INDUCTION; SIGNATURE; TARGETS; TUMORS;

D O I：

10.1016/j.molcel.2010.11.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains elusive. Using SILAC and quantitative mass spectrometry, we examined the effects of activation of the miR-17-92 cluster on global protein expression in neuroblastoma (NB) cells. Our results reveal cooperation between individual miR-17-92 miRNAs and implicate miR-17-92 in multiple hallmarks of cancer, including proliferation and cell adhesion. Most importantly, we show that miR-17-92 is a potent inhibitor of TGF-beta signaling. By functioning both upstream and downstream of pSMAD2, miR-17-92 activation triggers downregulation of multiple key effectors along the TGF-beta signaling cascade as well as direct inhibition of TGF-beta-responsive genes.

引用

页码：762 / 773

页数：12

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