Regulatory landscape and clinical implication of MBD3 in human malignant glioma.
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.
Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.|Biological Engineering and Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA.
Yi
Y
Cui
Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Jian
J
Li
Department of Neurology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Ling
L
Weng
School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.
Sara E
SE
Wirbisky
School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.
Jennifer L
JL
Freeman
Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Jingping
J
Liu
Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.|The Institute of Skull Base Surgery & Neuro-Oncology at Hunan, Xiangya Hospital, Changsha, Hunan 410008, China.
Qing
Q
Liu
Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.|The Institute of Skull Base Surgery & Neuro-Oncology at Hunan, Xiangya Hospital, Changsha, Hunan 410008, China.
Xianrui
X
Yuan
Biological Engineering and Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA.
Joseph
J
Irudayaraj
D044503:5-Methylcytosine / Q000031:analogs & derivatives / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006681:HLA-D Antigens / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D006681:HLA-D Antigens; C115369:MBD3 protein, human; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine
DNA methylation; MBD3; epigenetics; glioma; prognostic biomarker