Loss of tumor suppressive microRNA-31 enhances TRADD/NF-κB signaling in glioblastoma

Rajani Rajbhandari; Braden C. McFarland; Ashish Patel; Magda Gerigk; G. Kenneth Gray; Samuel C. Fehling; Markus Bredel; Nicolas F. Berbari; Hyunsoo Kim; Margaret P. Marks; Gordon P. Meares; Tanvi Sinha; Jeffrey Chuang; Etty N. Benveniste; Susan E. Nozell

doi:10.18632/oncotarget.4596

Loss of tumor suppressive microRNA-31 enhances TRADD/NF-κB signaling in glioblastoma

Rajani Rajbhandari, Braden C. McFarland, Ashish Patel, Magda Gerigk, G. Kenneth Gray, Samuel C. Fehling, Markus Bredel, Nicolas F. Berbari, Hyunsoo Kim, Margaret P. Marks, Gordon P. Meares, Tanvi Sinha, Jeffrey Chuang, Etty N. Benveniste, Susan E. Nozell

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

Glioblastomas (GBMs) are deadly tumors of the central nervous system. Most GBM exhibit homozygous deletions of the CDKN2A and CDKN2B tumor suppressors at 9p21.3, although loss of CDKN2A/B alone is insufficient to drive gliomagenesis. MIR31HG, which encodes microRNA-31 (miR-31), is a novel non-coding tumor suppressor positioned adjacent to CDKN2A/B at 9p21.3. We have determined that miR-31 expression is compromised in >72% of all GBM, and for patients, this predicts significantly shortened survival times independent of CDKN2A/B status. We show that miR-31 inhibits NF-κB signaling by targeting TRADD, its upstream activator. Moreover, upon reintroduction, miR-31 significantly reduces tumor burden and lengthens survival times in animal models. As such, our work identifies loss of miR-31 as a novel non-coding tumor-driving event in GBM.

Original language	English (US)
Pages (from-to)	17805-17816
Number of pages	12
Journal	Oncotarget
Volume	6
Issue number	19
DOIs	https://doi.org/10.18632/oncotarget.4596
State	Published - 2015
Externally published	Yes

Keywords

Glioblastoma
NF-κB
TRADD
microRNA-31

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.4596

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Rajbhandari, R., McFarland, B. C., Patel, A., Gerigk, M., Kenneth Gray, G., Fehling, S. C., Bredel, M., Berbari, N. F., Kim, H., Marks, M. P., Meares, G. P., Sinha, T., Chuang, J., Benveniste, E. N., & Nozell, S. E. (2015). Loss of tumor suppressive microRNA-31 enhances TRADD/NF-κB signaling in glioblastoma. Oncotarget, 6(19), 17805-17816. https://doi.org/10.18632/oncotarget.4596

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abstract = "Glioblastomas (GBMs) are deadly tumors of the central nervous system. Most GBM exhibit homozygous deletions of the CDKN2A and CDKN2B tumor suppressors at 9p21.3, although loss of CDKN2A/B alone is insufficient to drive gliomagenesis. MIR31HG, which encodes microRNA-31 (miR-31), is a novel non-coding tumor suppressor positioned adjacent to CDKN2A/B at 9p21.3. We have determined that miR-31 expression is compromised in >72% of all GBM, and for patients, this predicts significantly shortened survival times independent of CDKN2A/B status. We show that miR-31 inhibits NF-κB signaling by targeting TRADD, its upstream activator. Moreover, upon reintroduction, miR-31 significantly reduces tumor burden and lengthens survival times in animal models. As such, our work identifies loss of miR-31 as a novel non-coding tumor-driving event in GBM.",

keywords = "Glioblastoma, NF-κB, TRADD, microRNA-31",

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AU - Rajbhandari, Rajani

AU - McFarland, Braden C.

AU - Patel, Ashish

AU - Gerigk, Magda

AU - Kenneth Gray, G.

AU - Fehling, Samuel C.

AU - Bredel, Markus

AU - Berbari, Nicolas F.

AU - Kim, Hyunsoo

AU - Marks, Margaret P.

AU - Meares, Gordon P.

AU - Sinha, Tanvi

AU - Chuang, Jeffrey

AU - Benveniste, Etty N.

AU - Nozell, Susan E.

PY - 2015

Y1 - 2015

N2 - Glioblastomas (GBMs) are deadly tumors of the central nervous system. Most GBM exhibit homozygous deletions of the CDKN2A and CDKN2B tumor suppressors at 9p21.3, although loss of CDKN2A/B alone is insufficient to drive gliomagenesis. MIR31HG, which encodes microRNA-31 (miR-31), is a novel non-coding tumor suppressor positioned adjacent to CDKN2A/B at 9p21.3. We have determined that miR-31 expression is compromised in >72% of all GBM, and for patients, this predicts significantly shortened survival times independent of CDKN2A/B status. We show that miR-31 inhibits NF-κB signaling by targeting TRADD, its upstream activator. Moreover, upon reintroduction, miR-31 significantly reduces tumor burden and lengthens survival times in animal models. As such, our work identifies loss of miR-31 as a novel non-coding tumor-driving event in GBM.

AB - Glioblastomas (GBMs) are deadly tumors of the central nervous system. Most GBM exhibit homozygous deletions of the CDKN2A and CDKN2B tumor suppressors at 9p21.3, although loss of CDKN2A/B alone is insufficient to drive gliomagenesis. MIR31HG, which encodes microRNA-31 (miR-31), is a novel non-coding tumor suppressor positioned adjacent to CDKN2A/B at 9p21.3. We have determined that miR-31 expression is compromised in >72% of all GBM, and for patients, this predicts significantly shortened survival times independent of CDKN2A/B status. We show that miR-31 inhibits NF-κB signaling by targeting TRADD, its upstream activator. Moreover, upon reintroduction, miR-31 significantly reduces tumor burden and lengthens survival times in animal models. As such, our work identifies loss of miR-31 as a novel non-coding tumor-driving event in GBM.

KW - Glioblastoma

KW - NF-κB

KW - TRADD

KW - microRNA-31

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Loss of tumor suppressive microRNA-31 enhances TRADD/NF-κB signaling in glioblastoma

Abstract

Keywords

UN SDGs

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