MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma

被引:45
作者
Beckers, Anneleen [1 ]
Van Peer, Gert [1 ]
Carter, Daniel R. [2 ]
Gartlgruber, Moritz [3 ]
Herrmann, Carl [4 ,5 ]
Agarwal, Saurabh [6 ,7 ]
Helsmoortel, Hetty H. [1 ,8 ]
Althoff, Kristina [9 ,10 ]
Molenaar, Jan J. [11 ]
Cheung, Belamy B. [2 ]
Schulte, Johannes H. [3 ,9 ,10 ,12 ,13 ]
Benoit, Yves [8 ]
Shohet, Jason M. [6 ,7 ]
Westermann, Frank [3 ]
Marshall, Glenn M. [2 ]
Vandesompele, Jo [1 ]
De Preter, Katleen [1 ]
Speleman, Frank [1 ]
机构
[1] Univ Ghent, Ctr Med Genet CMGG, B-9000 Ghent, Belgium
[2] Lowy Canc Res Ctr, Childrens Canc Inst Australia Med Res, Randwick, NSW 2031, Australia
[3] German Canc Res Ctr, Div Neuroblastoma Genom, D-69120 Heidelberg, Germany
[4] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany
[5] Heidelberg Univ, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany
[6] Baylor Coll Med, Div Pediat Hematol Oncol, Houston, TX 77030 USA
[7] Baylor Coll Med, Dept Pediat, Ctr Cell & Gene Therapy, Houston, TX 77030 USA
[8] Ghent Univ Hosp, Dept Pediat Hematol Oncol & Stem Cell Transplanta, B-9000 Ghent, Belgium
[9] Univ Childrens Hosp Essen, Dept Pediat Oncol & Hematol, D-45147 Essen, Germany
[10] German Consortium Translat Canc Res DKTK, Essen, Germany
[11] Univ Amsterdam, Acad Med Ctr, Dept Oncogen, NL-1105 AZ Amsterdam, Netherlands
[12] Univ Duisburg Essen, West German Canc Ctr WTZ, Translat Neurooncol, D-45147 Essen, Germany
[13] Univ Duisburg Essen, Ctr Med Biotechnol, D-45147 Essen, Germany
基金
澳大利亚国家健康与医学研究理事会;
关键词
MicroRNA; Integrative analysis; Cross-species; CELL-PROLIFERATION; RELATIVE QUANTIFICATION; FEEDBACK LOOP; MICRORNAS; IDENTIFICATION; EXPRESSION; REVEALS; PROTEIN; GENES; INFORMATION;
D O I
10.1016/j.canlet.2015.06.015
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
LIN28B has been identified as an oncogene in various tumor entities, including neuroblastoma, a childhood cancer that originates from neural crest-derived cells, and is characterized by amplification of the MYCN oncogene. Recently, elevated LIN28B expression levels were shown to contribute to neuroblastoma tumorigenesis via let-7 dependent de-repression of MYCN. However, additional insight in the regulation of LIN28B in neuroblastoma is lacking. Therefore, we have performed a comprehensive analysis of the regulation of LIN28B in neuroblastoma, with a specific focus on the contribution of miRNAs. We show that MYCN regulates LIN28B expression in neuroblastoma tumors via two distinct parallel mechanisms. First, through an unbiased LIN28B-3'UTR reporter screen, we found that miR-26a-5p and miR-26b-5p regulate LIN28B expression. Next, we demonstrated that MYCN indirectly affects the expression of miR-26a-5p, and hence regulates LIN28B, therefore establishing an MYCN-miR-26a-5p-LIN28B regulatory axis. Second, we provide evidence that MYCN regulates LIN28B expression via interaction with the LIN28B promoter, establishing a direct MYCN-LIN28B regulatory axis. We believe that these findings mark LIN28B as an important effector of the MYCN oncogenic phenotype and underline the importance of MYCN-regulated miRNAs in establishing the MYCN-driven oncogenic process. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:123 / 132
页数:10
相关论文
共 39 条
[1]   A Cre-conditional MYCN-driven neuroblastoma mouse model as an improved tool for preclinical studies [J].
Althoff, K. ;
Beckers, A. ;
Bell, E. ;
Nortmeyer, M. ;
Thor, T. ;
Spruessel, A. ;
Lindner, S. ;
De Preter, K. ;
Florin, A. ;
Heukamp, L. C. ;
Klein-Hitpass, L. ;
Astrahantseff, K. ;
Kumps, C. ;
Speleman, F. ;
Eggert, A. ;
Westermann, F. ;
Schramm, A. ;
Schulte, J. H. .
ONCOGENE, 2015, 34 (26) :3357-3368
[2]   The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments [J].
Bustin, Stephen A. ;
Benes, Vladimir ;
Garson, Jeremy A. ;
Hellemans, Jan ;
Huggett, Jim ;
Kubista, Mikael ;
Mueller, Reinhold ;
Nolan, Tania ;
Pfaffl, Michael W. ;
Shipley, Gregory L. ;
Vandesompele, Jo ;
Wittwer, Carl T. .
CLINICAL CHEMISTRY, 2009, 55 (04) :611-622
[3]   MicroRNA-cancer connection: The beginning of a new tale [J].
Calin, George Adrian ;
Croce, Carlo Maria .
CANCER RESEARCH, 2006, 66 (15) :7390-7394
[4]   MicroRNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer [J].
Chang, Kah Hoong ;
Mestdagh, Pieter ;
Vandesompele, Jo ;
Kerin, Michael J. ;
Miller, Nicola .
BMC CANCER, 2010, 10
[5]   Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation [J].
Chang, Tsung-Cheng ;
Zeiteis, Lauren R. ;
Hwang, Hun-Way ;
Chivukula, Raghu R. ;
Wentzel, Erik A. ;
Dews, Michael ;
Jung, Jason ;
Gao, Ping ;
Dang, Chi V. ;
Beer, Michael A. ;
Thomas-Tikhonenko, Andrei ;
Mendell, Joshua T. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (09) :3384-3389
[6]   Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps [J].
Chi, Sung Wook ;
Zang, Julie B. ;
Mele, Aldo ;
Darnell, Robert B. .
NATURE, 2009, 460 (7254) :479-486
[7]   N-Myc Regulates Expression of Pluripotency Genes in Neuroblastoma Including lif, klf2, klf4, and lin28b [J].
Cotterman, Rebecca ;
Knoepfler, Paul S. .
PLOS ONE, 2009, 4 (06)
[8]   N-Myc Regulates a Widespread Euchromatic Program in the Human Genome Partially Independent of Its Role as a Classical Transcription Factor [J].
Cotterman, Rebecca ;
Jin, Victor X. ;
Krig, Sheryl R. ;
Lemen, Jessica M. ;
Wey, Alice ;
Farnham, Peggy J. ;
Knoepfler, Paul S. .
CANCER RESEARCH, 2008, 68 (23) :9654-9662
[9]   MicroRNAs in Cancer [J].
Di Leva, Gianpiero ;
Garofalo, Michela ;
Croce, Carlo M. .
ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 9, 2014, 9 :287-314
[10]  
Garzon R, 2009, ANNU REV MED, V60, P167, DOI [10.1146/annurev.med.59.053006.104707, 10.1146/annurev.pathol.4.110807.092222]