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Alternative Splicing of MXD3 and Its Regulation of MXD3 Levels in Glioblastoma

The transcription factor MXD3 is an atypical member of the MYC/MAX/MXD transcriptional network and has been previously shown to be an important regulator of cell proliferation. MXD3 has been shown to be overexpressed and to be required for medulloblastoma and acute lymphoblastic leukemia cell prolif...

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Autores principales: Ngo, Tin, Corrales, Abraham, Bourne, Traci, Elmojahid, Samir, Lam, Kit S., Díaz, Elva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390498/
https://www.ncbi.nlm.nih.gov/pubmed/30838212
http://dx.doi.org/10.3389/fmolb.2019.00005
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author Ngo, Tin
Corrales, Abraham
Bourne, Traci
Elmojahid, Samir
Lam, Kit S.
Díaz, Elva
author_facet Ngo, Tin
Corrales, Abraham
Bourne, Traci
Elmojahid, Samir
Lam, Kit S.
Díaz, Elva
author_sort Ngo, Tin
collection PubMed
description The transcription factor MXD3 is an atypical member of the MYC/MAX/MXD transcriptional network and has been previously shown to be an important regulator of cell proliferation. MXD3 has been shown to be overexpressed and to be required for medulloblastoma and acute lymphoblastic leukemia cell proliferation. In this study we leveraged datasets from The Cancer Genome Atlas to examine MXD3 across several cancers. We find that MXD3 transcripts are significantly overexpressed in ~72% of the available datasets. The gene itself is not frequently altered, while the promoter appears to be hypomethylated. We examine the possibility that aberrant regulation of the MXD3 message is the cause of abnormal MXD3 expression across cancers. Specifically, we looked at MXD3 alternative splicing in glioblastoma multiforme (GBM) and find notable functional differences between the splice variants. The 3′UTR confers differential message stability. Furthermore, the different coding sequences lead to different protein stabilities and localizations. Altogether, these data extend our knowledge of MXD3 in the context of human cancers while characterizing a previously unstudied splice variant of MXD3.
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spelling pubmed-63904982019-03-05 Alternative Splicing of MXD3 and Its Regulation of MXD3 Levels in Glioblastoma Ngo, Tin Corrales, Abraham Bourne, Traci Elmojahid, Samir Lam, Kit S. Díaz, Elva Front Mol Biosci Molecular Biosciences The transcription factor MXD3 is an atypical member of the MYC/MAX/MXD transcriptional network and has been previously shown to be an important regulator of cell proliferation. MXD3 has been shown to be overexpressed and to be required for medulloblastoma and acute lymphoblastic leukemia cell proliferation. In this study we leveraged datasets from The Cancer Genome Atlas to examine MXD3 across several cancers. We find that MXD3 transcripts are significantly overexpressed in ~72% of the available datasets. The gene itself is not frequently altered, while the promoter appears to be hypomethylated. We examine the possibility that aberrant regulation of the MXD3 message is the cause of abnormal MXD3 expression across cancers. Specifically, we looked at MXD3 alternative splicing in glioblastoma multiforme (GBM) and find notable functional differences between the splice variants. The 3′UTR confers differential message stability. Furthermore, the different coding sequences lead to different protein stabilities and localizations. Altogether, these data extend our knowledge of MXD3 in the context of human cancers while characterizing a previously unstudied splice variant of MXD3. Frontiers Media S.A. 2019-02-19 /pmc/articles/PMC6390498/ /pubmed/30838212 http://dx.doi.org/10.3389/fmolb.2019.00005 Text en Copyright © 2019 Ngo, Corrales, Bourne, Elmojahid, Lam and Díaz. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Ngo, Tin
Corrales, Abraham
Bourne, Traci
Elmojahid, Samir
Lam, Kit S.
Díaz, Elva
Alternative Splicing of MXD3 and Its Regulation of MXD3 Levels in Glioblastoma
title Alternative Splicing of MXD3 and Its Regulation of MXD3 Levels in Glioblastoma
title_full Alternative Splicing of MXD3 and Its Regulation of MXD3 Levels in Glioblastoma
title_fullStr Alternative Splicing of MXD3 and Its Regulation of MXD3 Levels in Glioblastoma
title_full_unstemmed Alternative Splicing of MXD3 and Its Regulation of MXD3 Levels in Glioblastoma
title_short Alternative Splicing of MXD3 and Its Regulation of MXD3 Levels in Glioblastoma
title_sort alternative splicing of mxd3 and its regulation of mxd3 levels in glioblastoma
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390498/
https://www.ncbi.nlm.nih.gov/pubmed/30838212
http://dx.doi.org/10.3389/fmolb.2019.00005
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