STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA

被引：105

作者：

Chen, An-Jou ^{[1
,2
,3
]}

Paik, Ji-Hye ^{[1
,2
,3
]}

Zhang, Hailei ^{[1
,2
]}

Shukla, Sachet A. ^{[1
,2
]}

Mortensen, Richard ^{[4
]}

Hu, Jian ^{[1
,2
,3
,5
]}

Ying, Haoqiang ^{[1
,2
,3
,5
]}

Hu, Baoli ^{[1
,2
,5
]}

Hurt, Jessica ^{[6
]}

Farny, Natalie ^{[6
]}

Dong, Caroline ^{[1
,2
]}

Xiao, Yonghong ^{[1
,2
]}

Wang, Y. Alan ^{[1
,2
,5
]}

Silver, Pamela A. ^{[6
]}

Chin, Lynda ^{[1
,2
,5
,7
]}

Vasudevan, Shobha ^{[4
]}

DePinho, Ronald A. ^{[1
,2
,3
,8
]}

机构：

[1] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[6] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02115 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

来源：

GENES & DEVELOPMENT | 2012年 / 26卷 / 13期

关键词：

cancer; GBM; miRNA; p53; TGF beta; QKI; GROWTH-FACTOR-BETA; MESSENGER-RNA; SIGNAL-TRANSDUCTION; MIR-17-92; CLUSTER; TGF-BETA; P53; CELL; MICRORNAS; GENE; IDENTIFICATION;

D O I：

10.1101/gad.189001.112

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Multidimensional cancer genome analysis and validation has defined Quaking (QKI), a member of the signal transduction and activation of RNA (STAR) family of RNA-binding proteins, as a novel glioblastoma multiforme (GBM) tumor suppressor. Here, we establish that p53 directly regulates QKI gene expression, and QKI protein associates with and leads to the stabilization of miR-20a; miR-20a, in turn, regulates TGF beta R2 and the TGF beta signaling network. This pathway circuitry is substantiated by in silico epistasis analysis of its components in the human GBM TCGA (The Cancer Genome Atlas Project) collection and by their gain- and loss-of-function interactions in in vitro and in vivo complementation studies. This p53-QKI-miR-20a-TGF beta pathway expands our understanding of the p53 tumor suppression network in cancer and reveals a novel tumor suppression mechanism involving regulation of specific cancer-relevant microRNAs.

引用

页码：1459 / 1472

页数：14

共 56 条

[1] Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia [J].

Aberg, Karolina ;

Saetre, Peter ;

Jareborg, Niclas ;

Jazin, Elena .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (19) :7482-7487

[2] Epidermal growth factor receptor and Ink4a/Arf:: Convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis [J].

Bachoo, RM ;

Maher, EA ;

Ligon, KL ;

Sharpless, NE ;

Chan, SS ;

You, MJJ ;

Tang, Y ;

DeFrances, J ;

Stover, E ;

Weissleder, R ;

Rowitch, DH ;

Louis, DN ;

DePinho, RA .

CANCER CELL, 2002, 1 (03) :269-277

[3] The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cells [J].

Busa, R. ;

Paronetto, M. P. ;

Farini, D. ;

Pierantozzi, E. ;

Botti, F. ;

Angelini, D. F. ;

Attisani, F. ;

Vespasiani, G. ;

Sette, C. .

ONCOGENE, 2007, 26 (30) :4372-4382

[4] Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia [J].

Calin, GA ;

Dumitru, CD ;

Shimizu, M ;

Bichi, R ;

Zupo, S ;

Noch, E ;

Aldler, H ;

Rattan, S ;

Keating, M ;

Rai, K ;

Rassenti, L ;

Kipps, T ;

Negrini, M ;

Bullrich, F ;

Croce, CM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (24) :15524-15529

[5] Structure-function analysis of Qk1:: a lethal point mutation in mouse quaking prevents homodimerization [J].

Chen, TP ;

Richard, S .

MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (08) :4863-4871

[6] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[7] Temporal dissection of p53 function in vitro and in vivo [J].

Christophorou, MA ;

Martin-Zanca, D ;

Soucek, L ;

Lawlor, ER ;

Brown-Swigart, L ;

Verschuren, EW ;

Evan, GI .

NATURE GENETICS, 2005, 37 (07) :718-726

[8] Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster [J].

Dews, Michael ;

Homayouni, Asal ;

Yu, Duonan ;

Murphy, Danielle ;

Sevignani, Cinzia ;

Wentzel, Erik ;

Furth, Emma E. ;

Lee, William M. ;

Enders, Greg H. ;

T Mendell, Joshua ;

Thomas-Tikhonenko, Andrei .

NATURE GENETICS, 2006, 38 (09) :1060-1065

[9] The Myc-miR-17∼92 Axis Blunts TGFβ Signaling and Production of Multiple TGFβ-Dependent Antiangiogenic Factors [J].

Dews, Michael ;

Fox, Jamie L. ;

Hultine, Stacy ;

Sundaram, Prema ;

Wang, Wenge ;

Liu, Yingqiu Y. ;

Furth, Emma ;

Enders, Gregory H. ;

El-Deiry, Wafik ;

Schelter, Janell M. ;

Cleary, Michele A. ;

Thomas-Tikhonenko, Andrei .

CANCER RESEARCH, 2010, 70 (20) :8233-8246

[10] The quaking gene product necessary in embryogenesis and myelination combines features of RNA binding and signal transduction proteins [J].

Ebersole, TA ;

Chen, Q ;

Justice, MJ ;

Artzt, K .

NATURE GENETICS, 1996, 12 (03) :260-265

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