Role of MXD3 in proliferation of DAOY human medulloblastoma cells

Gustavo Barisone, Tin Ngo, Martin Tran, Daniel Cortes, Mehdi H. Shahi, Tuong Vi Nguyen, Daniel Perez-Lanza, Wanna Matayasuwan, Elva D Diaz

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

A subset of medulloblastomas, the most common brain tumor in children, is hypothesized to originate from granule neuron precursors (GNPs) in which the sonic hedgehog (SHH) pathway is over-activated. MXD3, a basic helix-look-helix zipper transcription factor of the MAD family, has been reported to be upregulated during postnatal cerebellar development and to promote GNP proliferation and MYCN expression. Mxd3 is upregulated in mouse models of medulloblastoma as well as in human medulloblastomas. Therefore, we hypothesize that MXD3 plays a role in the cellular events that lead to medulloblastoma biogenesis. In agreement with its proliferative role in GNPs, MXD3 knock-down in DAOY cells resulted in decreased proliferation. Sustained overexpression of MXD3 resulted in decreased cell numbers due to increased apoptosis and cell cycle arrest. Structure-function analysis revealed that the Sin3 interacting domain, the basic domain, and binding to E-boxes are essential for this activity. Microarray-based expression analysis indicated up-regulation of 84 genes and down-regulation of 47 genes. Potential direct MXD3 target genes were identified by ChIP-chip. Our results suggest that MXD3 is necessary for DAOY medulloblastoma cell proliferation. However, increased level and/or duration of MXD3 expression ultimately reduces cell numbers via increased cell death and cell cycle arrest.

Original languageEnglish (US)
Article numbere38508
JournalPLoS One
Volume7
Issue number7
DOIs
StatePublished - Jul 10 2012

Fingerprint

Medulloblastoma
Neurons
granules
Genes
neurons
Cells
Cell Cycle Checkpoints
genes
Erinaceidae
postnatal development
Fasteners
Cell proliferation
Cell death
cells
Microarrays
Cell Count
cell death
Tumors
Brain
cell proliferation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Barisone, G., Ngo, T., Tran, M., Cortes, D., Shahi, M. H., Nguyen, T. V., ... Diaz, E. D. (2012). Role of MXD3 in proliferation of DAOY human medulloblastoma cells. PLoS One, 7(7), [e38508]. https://doi.org/10.1371/journal.pone.0038508

Role of MXD3 in proliferation of DAOY human medulloblastoma cells. / Barisone, Gustavo; Ngo, Tin; Tran, Martin; Cortes, Daniel; Shahi, Mehdi H.; Nguyen, Tuong Vi; Perez-Lanza, Daniel; Matayasuwan, Wanna; Diaz, Elva D.

In: PLoS One, Vol. 7, No. 7, e38508, 10.07.2012.

Research output: Contribution to journalArticle

Barisone, G, Ngo, T, Tran, M, Cortes, D, Shahi, MH, Nguyen, TV, Perez-Lanza, D, Matayasuwan, W & Diaz, ED 2012, 'Role of MXD3 in proliferation of DAOY human medulloblastoma cells', PLoS One, vol. 7, no. 7, e38508. https://doi.org/10.1371/journal.pone.0038508
Barisone G, Ngo T, Tran M, Cortes D, Shahi MH, Nguyen TV et al. Role of MXD3 in proliferation of DAOY human medulloblastoma cells. PLoS One. 2012 Jul 10;7(7). e38508. https://doi.org/10.1371/journal.pone.0038508
Barisone, Gustavo ; Ngo, Tin ; Tran, Martin ; Cortes, Daniel ; Shahi, Mehdi H. ; Nguyen, Tuong Vi ; Perez-Lanza, Daniel ; Matayasuwan, Wanna ; Diaz, Elva D. / Role of MXD3 in proliferation of DAOY human medulloblastoma cells. In: PLoS One. 2012 ; Vol. 7, No. 7.
@article{a72bab7376534a34941233a261d64f40,
title = "Role of MXD3 in proliferation of DAOY human medulloblastoma cells",
abstract = "A subset of medulloblastomas, the most common brain tumor in children, is hypothesized to originate from granule neuron precursors (GNPs) in which the sonic hedgehog (SHH) pathway is over-activated. MXD3, a basic helix-look-helix zipper transcription factor of the MAD family, has been reported to be upregulated during postnatal cerebellar development and to promote GNP proliferation and MYCN expression. Mxd3 is upregulated in mouse models of medulloblastoma as well as in human medulloblastomas. Therefore, we hypothesize that MXD3 plays a role in the cellular events that lead to medulloblastoma biogenesis. In agreement with its proliferative role in GNPs, MXD3 knock-down in DAOY cells resulted in decreased proliferation. Sustained overexpression of MXD3 resulted in decreased cell numbers due to increased apoptosis and cell cycle arrest. Structure-function analysis revealed that the Sin3 interacting domain, the basic domain, and binding to E-boxes are essential for this activity. Microarray-based expression analysis indicated up-regulation of 84 genes and down-regulation of 47 genes. Potential direct MXD3 target genes were identified by ChIP-chip. Our results suggest that MXD3 is necessary for DAOY medulloblastoma cell proliferation. However, increased level and/or duration of MXD3 expression ultimately reduces cell numbers via increased cell death and cell cycle arrest.",
author = "Gustavo Barisone and Tin Ngo and Martin Tran and Daniel Cortes and Shahi, {Mehdi H.} and Nguyen, {Tuong Vi} and Daniel Perez-Lanza and Wanna Matayasuwan and Diaz, {Elva D}",
year = "2012",
month = "7",
day = "10",
doi = "10.1371/journal.pone.0038508",
language = "English (US)",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - Role of MXD3 in proliferation of DAOY human medulloblastoma cells

AU - Barisone, Gustavo

AU - Ngo, Tin

AU - Tran, Martin

AU - Cortes, Daniel

AU - Shahi, Mehdi H.

AU - Nguyen, Tuong Vi

AU - Perez-Lanza, Daniel

AU - Matayasuwan, Wanna

AU - Diaz, Elva D

PY - 2012/7/10

Y1 - 2012/7/10

N2 - A subset of medulloblastomas, the most common brain tumor in children, is hypothesized to originate from granule neuron precursors (GNPs) in which the sonic hedgehog (SHH) pathway is over-activated. MXD3, a basic helix-look-helix zipper transcription factor of the MAD family, has been reported to be upregulated during postnatal cerebellar development and to promote GNP proliferation and MYCN expression. Mxd3 is upregulated in mouse models of medulloblastoma as well as in human medulloblastomas. Therefore, we hypothesize that MXD3 plays a role in the cellular events that lead to medulloblastoma biogenesis. In agreement with its proliferative role in GNPs, MXD3 knock-down in DAOY cells resulted in decreased proliferation. Sustained overexpression of MXD3 resulted in decreased cell numbers due to increased apoptosis and cell cycle arrest. Structure-function analysis revealed that the Sin3 interacting domain, the basic domain, and binding to E-boxes are essential for this activity. Microarray-based expression analysis indicated up-regulation of 84 genes and down-regulation of 47 genes. Potential direct MXD3 target genes were identified by ChIP-chip. Our results suggest that MXD3 is necessary for DAOY medulloblastoma cell proliferation. However, increased level and/or duration of MXD3 expression ultimately reduces cell numbers via increased cell death and cell cycle arrest.

AB - A subset of medulloblastomas, the most common brain tumor in children, is hypothesized to originate from granule neuron precursors (GNPs) in which the sonic hedgehog (SHH) pathway is over-activated. MXD3, a basic helix-look-helix zipper transcription factor of the MAD family, has been reported to be upregulated during postnatal cerebellar development and to promote GNP proliferation and MYCN expression. Mxd3 is upregulated in mouse models of medulloblastoma as well as in human medulloblastomas. Therefore, we hypothesize that MXD3 plays a role in the cellular events that lead to medulloblastoma biogenesis. In agreement with its proliferative role in GNPs, MXD3 knock-down in DAOY cells resulted in decreased proliferation. Sustained overexpression of MXD3 resulted in decreased cell numbers due to increased apoptosis and cell cycle arrest. Structure-function analysis revealed that the Sin3 interacting domain, the basic domain, and binding to E-boxes are essential for this activity. Microarray-based expression analysis indicated up-regulation of 84 genes and down-regulation of 47 genes. Potential direct MXD3 target genes were identified by ChIP-chip. Our results suggest that MXD3 is necessary for DAOY medulloblastoma cell proliferation. However, increased level and/or duration of MXD3 expression ultimately reduces cell numbers via increased cell death and cell cycle arrest.

UR - http://www.scopus.com/inward/record.url?scp=84863676455&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863676455&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0038508

DO - 10.1371/journal.pone.0038508

M3 - Article

C2 - 22808009

AN - SCOPUS:84863676455

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e38508

ER -