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, Erxi Wu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRa and PDGFRß signaling in MB biology remain poorly understood.Here, we report the subgroup specific expression of PDGFRa and PDGFRß and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRß but not PDGFRa, is involved in PDGFRß signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRß and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRß 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 PDGFRß-driven signaling cascade and a potential therapeutic target.

Original languageEnglish (US)
Pages (from-to)2709-2724
Number of pages16
JournalOncotarget
Volume6
Issue number5
DOIs
StatePublished - Jan 1 2015

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Platelet-Derived Growth Factor Receptors
Medulloblastoma
MicroRNAs
Cell Proliferation
Cell Movement
Cell Death

Keywords

  • JAG2
  • PDGFR
  • c-MYC
  • medulloblastoma
  • miR-1280

ASJC Scopus subject areas

  • Oncology

Cite this

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. https://doi.org/10.18632/oncotarget.2779

A microRNA-1280/JAG2 network comprises a novel biological target in high-risk medulloblastoma. / Wang, Fengfei; Remke, Marc; Bhat, Kruttika; Wong, Eric T.; Zhou, Shuang; Ramaswamy, Vijay; Dubuc, Adrian; Fonkem, Ekokobe; Salem, Saeed; Zhang, Hongbing; Hsieh, Tze chen; O'Rourke, Stephen T.; Wu, Lizi; Li, David W.; Hawkins, Cynthia; Kohane, Isaac S.; Wu, Joseph M.; Wu, Min; Taylor, Michael D.; Wu, Erxi.

In: Oncotarget, Vol. 6, No. 5, 01.01.2015, p. 2709-2724.

Research output: Contribution to journalArticle

Wang, F, Remke, M, Bhat, K, Wong, ET, Zhou, S, Ramaswamy, V, Dubuc, A, Fonkem, E, Salem, S, Zhang, H, Hsieh, TC, O'Rourke, ST, Wu, L, Li, DW, Hawkins, C, Kohane, IS, Wu, JM, Wu, M, Taylor, MD & Wu, E 2015, 'A microRNA-1280/JAG2 network comprises a novel biological target in high-risk medulloblastoma', Oncotarget, vol. 6, no. 5, pp. 2709-2724. https://doi.org/10.18632/oncotarget.2779
Wang, Fengfei ; Remke, Marc ; Bhat, Kruttika ; Wong, Eric T. ; Zhou, Shuang ; Ramaswamy, Vijay ; Dubuc, Adrian ; Fonkem, Ekokobe ; Salem, Saeed ; Zhang, Hongbing ; Hsieh, Tze chen ; O'Rourke, Stephen T. ; Wu, Lizi ; Li, David W. ; Hawkins, Cynthia ; Kohane, Isaac S. ; Wu, Joseph M. ; Wu, Min ; Taylor, Michael D. ; Wu, Erxi. / A microRNA-1280/JAG2 network comprises a novel biological target in high-risk medulloblastoma. In: Oncotarget. 2015 ; Vol. 6, No. 5. pp. 2709-2724.
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abstract = "Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRa and PDGFR{\ss} signaling in MB biology remain poorly understood.Here, we report the subgroup specific expression of PDGFRa and PDGFR{\ss} and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFR{\ss} but not PDGFRa, is involved in PDGFR{\ss} signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFR{\ss} and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFR{\ss} 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 PDGFR{\ss}-driven signaling cascade and a potential therapeutic target.",
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