NYMC Faculty Publications
First Page
2709
Last Page
2724
Document Type
Article
Publication Date
12-17-2014
Department
Biochemistry and Molecular Biology
Keywords
Antineoplastic Agents, Cell Death, Cell Line, Tumor, Cell Movement, Cell Proliferation, Cerebellar Neoplasms, Computational Biology, Dose-Response Relationship, Drug, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Intercellular Signaling Peptides and Proteins, Jagged-2 Protein, Medulloblastoma, Membrane Proteins, MicroRNAs, Molecular Targeted Therapy, Neoplasm Invasiveness, Prognosis, Proto-Oncogene Proteins c-myc, RNA Interference, RNAi Therapeutics, Receptor, Platelet-Derived Growth Factor alpha, Receptor, Platelet-Derived Growth Factor beta, Signal Transduction, Transfection
Disciplines
Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology
Abstract
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.
Recommended Citation
Wang, F., Remke, M., Bhat, K., Wong, E. T., Zhou, S., Ramaswamy, V., … Wu, E. (2015). A microRNA-1280/JAG2 network comprises a novel biological target in high-risk medulloblastoma. Oncotarget, 6(5), 2709–2724. doi:10.18632/oncotarget.2779
Publisher's Statement
Originally published in Oncotarget. Licensed under CC-BY 4.0. https://doi.org/10.18632/oncotarget.2779
Included in
Amino Acids, Peptides, and Proteins Commons, Biochemistry, Biophysics, and Structural Biology Commons
Comments
Please see the work itself for the complete list of authors.