Abstract
In this article we inspect the roles and functions of the methyl-CpG-binding domain protein 3 (MBD3) in human malignant glioma, to assess its potential as an epigenetic biomarker for prognosis. The regulatory effects of MBD3 on glioma transcriptome were first profiled by high-throughput microarray. Our results indicate that MBD3 is involved in both transcriptional activation and repression. Furthermore, MBD3 fine-controls a spectrum of proteins critical for cellular metabolism and proliferation, thereby contributing to an exquisite anti-glioma network. Specifically, the expression of MHC class II molecules was found to positively correlate with MBD3, which provides new insight into the immune escape of gliomagenesis. In addition, MBD3 participates in constraining a number of oncogenic non-coding RNAs whose over-activation could drive cells into excessive growth and higher malignancy. Having followed up a pilot cohort, we noted that the survival of malignant glioma patients was proportional to the content of MBD3 and 5-hydroxymethylcytosine (5hmC) in their tumor cells. The progression-free survival (PFS) and overall survival (OS) were relatively poor for patients with lower amount of MBD3 and 5hmC in the tissue biopsies. Taken together, this work enriches our understanding of the mechanistic involvement of MBD3 in malignant glioma.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 81698-81714 |
| Number of pages | 17 |
| Journal | Oncotarget |
| Volume | 7 |
| Issue number | 49 |
| DOIs | |
| State | Published - Jan 1 2016 |
| Externally published | Yes |
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Keywords
- DNA methylation
- Epigenetics
- Glioma
- MBD3
- Prognostic biomarker
ASJC Scopus subject areas
- Oncology
Cite this
Regulatory landscape and clinical implication of MBD3 in human malignant glioma. / Cui, Yi; Li, Jian; Weng, Ling; Wirbisky, Sara E.; Freeman, Jennifer L.; Liu, Jingping; Liu, Qing; Yuan, Xianrui; Irudayaraj, Joseph.
In: Oncotarget, Vol. 7, No. 49, 01.01.2016, p. 81698-81714.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulatory landscape and clinical implication of MBD3 in human malignant glioma
AU - Cui, Yi
AU - Li, Jian
AU - Weng, Ling
AU - Wirbisky, Sara E.
AU - Freeman, Jennifer L.
AU - Liu, Jingping
AU - Liu, Qing
AU - Yuan, Xianrui
AU - Irudayaraj, Joseph
PY - 2016/1/1
Y1 - 2016/1/1
N2 - In this article we inspect the roles and functions of the methyl-CpG-binding domain protein 3 (MBD3) in human malignant glioma, to assess its potential as an epigenetic biomarker for prognosis. The regulatory effects of MBD3 on glioma transcriptome were first profiled by high-throughput microarray. Our results indicate that MBD3 is involved in both transcriptional activation and repression. Furthermore, MBD3 fine-controls a spectrum of proteins critical for cellular metabolism and proliferation, thereby contributing to an exquisite anti-glioma network. Specifically, the expression of MHC class II molecules was found to positively correlate with MBD3, which provides new insight into the immune escape of gliomagenesis. In addition, MBD3 participates in constraining a number of oncogenic non-coding RNAs whose over-activation could drive cells into excessive growth and higher malignancy. Having followed up a pilot cohort, we noted that the survival of malignant glioma patients was proportional to the content of MBD3 and 5-hydroxymethylcytosine (5hmC) in their tumor cells. The progression-free survival (PFS) and overall survival (OS) were relatively poor for patients with lower amount of MBD3 and 5hmC in the tissue biopsies. Taken together, this work enriches our understanding of the mechanistic involvement of MBD3 in malignant glioma.
AB - In this article we inspect the roles and functions of the methyl-CpG-binding domain protein 3 (MBD3) in human malignant glioma, to assess its potential as an epigenetic biomarker for prognosis. The regulatory effects of MBD3 on glioma transcriptome were first profiled by high-throughput microarray. Our results indicate that MBD3 is involved in both transcriptional activation and repression. Furthermore, MBD3 fine-controls a spectrum of proteins critical for cellular metabolism and proliferation, thereby contributing to an exquisite anti-glioma network. Specifically, the expression of MHC class II molecules was found to positively correlate with MBD3, which provides new insight into the immune escape of gliomagenesis. In addition, MBD3 participates in constraining a number of oncogenic non-coding RNAs whose over-activation could drive cells into excessive growth and higher malignancy. Having followed up a pilot cohort, we noted that the survival of malignant glioma patients was proportional to the content of MBD3 and 5-hydroxymethylcytosine (5hmC) in their tumor cells. The progression-free survival (PFS) and overall survival (OS) were relatively poor for patients with lower amount of MBD3 and 5hmC in the tissue biopsies. Taken together, this work enriches our understanding of the mechanistic involvement of MBD3 in malignant glioma.
KW - DNA methylation
KW - Epigenetics
KW - Glioma
KW - MBD3
KW - Prognostic biomarker
UR - http://www.scopus.com/inward/record.url?scp=85000916630&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85000916630&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.13173
DO - 10.18632/oncotarget.13173
M3 - Article
C2 - 27835581
AN - SCOPUS:85000916630
VL - 7
SP - 81698
EP - 81714
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 49
ER -