Regulatory landscape and clinical implication of MBD3 in human malignant glioma

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.

Glioma stem-like cells evade interferon suppression through MBD3/NuRD complex–mediated STAT1 downregulation

“…Our data demonstrate that MBD3, but not other components of the NuRD complex, is preferentially expressed in GSCs to promote GSC tumorigenicity. In contrast to our results, a recent study reported that MBD3 inhibits proliferation of the established GBM cell line SF767 ( Cui et al, 2016 ). We speculate that different culture conditions contribute to the inconsistent roles of MBD3 in malignant glioma cells.…”

Epigenetic modulator inhibition overcomes temozolomide chemoresistance and antagonizes tumor recurrence of glioblastoma

“…Finally, our observation that MBD3 inhibits neural differentiation of GSCs but maintains GSC self-renewal is somewhat discrepant from observations reported by Cui et al (46), who showed that MBD3 expression is lower in human GBM than in normal brain, and that MBD3 loss promotes brain tumor proliferation and migration. The study by Cui et al, however, analyzed the SF767 GBM line, which may account for the discrepancy.…”

DNA Methylation Readers and Cancer: Mechanistic and Therapeutic Applications

“…In clinical specimens obtained from pancreatic cancer patients, decreased MBD3 gene expression showed an association with poor patient survival (42). A similar observation was noted in malignant glioma where patient samples with reduced MBD3 expression showed a correlation with decreased overall survival and progression-free survival (43). Moreover, knockdown of MBD3 gene promoted cancer cell migration and invasion while overexpression inhibited those effects (42).…”