Document Type
Journal Article
Publication Date
3-30-2015
Journal
Oncotarget
Volume
6
Issue
14
Inclusive Pages
12141-55
DOI
10.18632/oncotarget.3716
Keywords
Antigens--genetics; Antigens--metabolism; Brain Stem Neoplasms--genetics; Glioma--genetics; Proteoglycans--genetics; Proteoglycans--metabolism
Abstract
Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis and are poorly understood brain cancers. Receptor tyrosine kinases stabilized by neuron-glial antigen 2 (NG2) protein are known to induce gliomagenesis. Here, we investigated NG2 expression in a cohort of DIPG specimens (n= 50). We demonstrate NG2 expression in the majority of DIPG specimens tested and determine that tumors harboring histone 3.3 mutation express the highest NG2 levels. We further demonstrate that microRNA 129-2 (miR129-2) is downregulated and hypermethylated in human DIPGs, resulting in the increased expression of NG2. Treatment with 5-Azacytidine, a methyltransferase inhibitor, results in NG2 downregulation in DIPG primary tumor cells in vitro. NG2 expression is altered (symmetric segregation) in mitotic human DIPG and mouse tumor cells. These mitotic cells co-express oligodendrocyte (Olig2) and astrocyte (glial fibrillary acidic protein, GFAP) markers, indicating lack of terminal differentiation. NG2 knockdown retards cellular migration in vitro, while NG2 expressing neurospheres are highly tumorigenic in vivo, resulting in rapid growth of pontine tumors. NG2 expression is targetable in vivo using miR129-2 indicating a potential avenue for therapeutic interventions. This data implicates NG2 as a molecule of interest in DIPGs especially those with H3.3 mutation.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Epub ahead of print
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of Impact Journals. Oncotarget.