Research Papers:

A microRNA-1280/JAG2 network comprises a novel biological target in high-risk medulloblastoma

Fengfei Wang _, Marc Remke, Kruttika Bhat, Eric T. Wong, Shuang Zhou, Vijay Ramaswamy, Adrian Dubuc, Ekokobe Fonkem, Saeed Salem, Hongbing Zhang, Tze-chen Hsieh, Stephen T. O'Rourke, Lizi Wu, David W. Li, Cynthia Hawkins, Isaac S. Kohane, Joseph M. Wu, Min Wu, Michael D. Taylor and Erxi Wu

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2015; 6:2709-2724. https://doi.org/10.18632/oncotarget.2779

Metrics: PDF 2299 views  |   HTML 3335 views  |   ?  


Fengfei Wang1,*, Marc Remke2,*, Kruttika Bhat1,*, Eric T. Wong3, Shuang Zhou1, Vijay Ramaswamy2, Adrian Dubuc2, Ekokobe Fonkem4, Saeed Salem5, Hongbing Zhang6, Tze-chen Hsieh7, Stephen T. O’Rourke1, Lizi Wu8, David W. Li9, Cynthia Hawkins10, Isaac S. Kohane11, Joseph M. Wu7, Min Wu12, Michael D. Taylor2, Erxi Wu1

1Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, USA

2Arthur and Sonia Labatt Brain Tumor Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1X8, Canada

3Brain Tumor Center & Neuro-Oncology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA

4Scott & White Neuroscience Institute, Texas A & M Health Science Center, Temple, TX 76508, USA

5Department of Computer Sciences, North Dakota State University, Fargo, ND 58105, USA

6Department of Physiology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100073, China

7Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA

8Department of Molecular Genetics and Microbiology, Shands Cancer Center, University of Florida, Gainesville, FL 32610, USA

9Department of Ophthalmology & Visual Sciences, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA

10Division of Pathology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada

11Informatics Program, Children’s Hospital Boston, Harvard Medical School, Boston 02115, MA, USA

12Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, ND 58202, USA

*These authors have contributed equally to this work

Correspondence to:

Michael D. Taylor, e-mail: [email protected]

Erxi Wu, e-mail: [email protected]

Keywords: PDGFR, c-MYC, JAG2, miR-1280, medulloblastoma, target therapy

Received: September 21, 2014     Accepted: November 19, 2014     Published: December 17, 2014


Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased expression of JAG2, a target of miR-1280, is associated with high metastatic dissemination at diagnosis and a poor outcome in MB patients. Our study may resolve the controversy on the role of PDGFRs in MB and unveils JAG2 as a key downstream effector of a PDGFRβ-driven signaling cascade and a potential therapeutic target.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 2779