Regulatory landscape and clinical implication of MBD3 in human malignant glioma
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Yi Cui1,5,*, Jian Li1,*, Ling Weng2, Sara E. Wirbisky4, Jennifer L. Freeman4, Jingping Liu1, Qing Liu1,3, Xianrui Yuan1,3, Joseph Irudayaraj5
1Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China
2Department of Neurology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China
3The Institute of Skull Base Surgery & Neuro-Oncology at Hunan, Xiangya Hospital, Changsha, Hunan 410008, China
4School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA
5Biological Engineering and Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA
*These authors have contributed equally to this work
Joseph Irudayaraj, email: [email protected]
Keywords: glioma, epigenetics, MBD3, DNA methylation, prognostic biomarker
Received: August 26, 2016 Accepted: October 19, 2016 Published: November 07, 2016
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.
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