Regulatory landscape and clinical implication of MBD3 in human malignant glioma.
Regulatory landscape and clinical implication of MBD3 in human malignant glioma.
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MBD3 在人类恶性胶质瘤中的监管格局和临床意义。
DOI：
10.18632/oncotarget.13173
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发表时间：
2016-12-06
期刊：
影响因子：
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通讯作者：
Irudayaraj J
中科院分区：
文献类型：
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作者：
Cui Y;Li J;Weng L;Wirbisky SE;Freeman JL;Liu J;Liu Q;Yuan X;Irudayaraj J
在本文中，我们检查甲基CpG结合域蛋白3（MBD 3）在人类恶性胶质瘤中的作用和功能，以评估其作为预后的表观遗传生物标志物的潜力。首次通过高通量芯片分析MBD 3对胶质瘤转录组的调控作用。我们的研究结果表明，MBD 3参与转录激活和抑制。此外，MBD 3精细控制对细胞代谢和增殖至关重要的蛋白质谱，从而有助于形成精致的抗神经胶质瘤网络。具体而言，发现MHC II类分子的表达与MBD 3正相关，这为胶质瘤形成的免疫逃逸提供了新的见解。此外，MBD 3参与限制许多致癌的非编码RNA，其过度活化可驱使细胞过度生长和更高的恶性度。在对一个试点队列进行随访后，我们注意到恶性胶质瘤患者的生存率与其肿瘤细胞中MBD 3和5-羟甲基胞嘧啶（5 hmC）的含量成正比。组织活检中MBD 3和5 hmC含量较低的患者的无进展生存期（PFS）和总生存期（OS）相对较差。总之，这项工作丰富了我们对MBD 3参与恶性胶质瘤机制的理解。
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.