Alternative splicing of MXD3 and its regulation of MXD3 levels in glioblastoma

Tin Ngo, Abraham Corrales, Traci Bourne, Samir Elmojahid, Kit Lam, Elva D Diaz

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number00005
JournalFrontiers in Molecular Biosciences
Volume6
Issue numberFEB
DOIs
StatePublished - Jan 1 2019

Fingerprint

Cell proliferation
Alternative Splicing
Glioblastoma
Genes
3' Untranslated Regions
Neoplasms
Transcription Factors
Cell Proliferation
Medulloblastoma
Protein Stability
Atlases
Gene Regulatory Networks
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Proteins
Genome
Datasets

Keywords

  • Alternative splicing
  • Glioblastoma
  • MXD3
  • MYC/MAX/MXD network
  • The Cancer Genome Atlas (TCGA)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

Cite this

Alternative splicing of MXD3 and its regulation of MXD3 levels in glioblastoma. / Ngo, Tin; Corrales, Abraham; Bourne, Traci; Elmojahid, Samir; Lam, Kit; Diaz, Elva D.

In: Frontiers in Molecular Biosciences, Vol. 6, No. FEB, 00005, 01.01.2019.

Research output: Contribution to journalArticle

Ngo, Tin ; Corrales, Abraham ; Bourne, Traci ; Elmojahid, Samir ; Lam, Kit ; Diaz, Elva D. / Alternative splicing of MXD3 and its regulation of MXD3 levels in glioblastoma. In: Frontiers in Molecular Biosciences. 2019 ; Vol. 6, No. FEB.
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