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Last update 23 Jan 2025

MBD3

Last update 23 Jan 2025

Basic Info

Synonyms

MBD3, methyl-CpG binding domain protein 3, Methyl-CpG-binding domain protein 3

+ [1]

Introduction

Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:12124384, PubMed:16428440, PubMed:28977666). Acts as transcriptional repressor and plays a role in gene silencing (PubMed:10947852, PubMed:18644863). Does not bind to methylated DNA by itself (PubMed:12124384, PubMed:16428440). Binds to a lesser degree DNA containing unmethylated CpG dinucleotides (PubMed:24307175). Recruits histone deacetylases and DNA methyltransferases.

Drugs associated with MBD3

HG-1254

Target

MBD3

Mechanism

MBD3 modulators

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MBD3

100 Translational Medicine associated with MBD3

0 Patents (Medical) associated with MBD3

284

Literatures (Medical) associated with MBD3

01 Jan 2025·Med

Inactivation of TACC2 epigenetically represses CDKN1A and confers sensitivity to CDK inhibitors

Article

Author: Bei, Jin-Xin ; Yuan, Bo-Yu ; Wang, Meng-Yao ; Zhong, Qian ; Xia, Tian-Liang ; Lin, Zhi-Rui ; Yuan, Li ; Zheng, Jian ; Liu, Yan-Min ; Lin, Dong-Xin ; Zhou, Ai-Jun ; Zeng, Mu-Sheng ; Zhang, Lan-Jun

BACKGROUNDThe genomic landscape of esophageal squamous cell carcinoma (ESCC) has been characterized extensively, but there remains a significant need for actionable targets and effective therapies.METHODSHere, we perform integrative analysis of genome-wide loss of heterozygosity and expression to identify potential tumor suppressor genes. The functions and mechanisms of one of the candidates, TACC2, are then explored both in vitro and in vivo, leading to the proposal of a therapeutic strategy based on the concept of synthetic lethality.FINDINGSWe reveal that the inactivation of TACC2, due to copy number loss and promoter hypermethylation, is associated with poor prognosis in ESCC patients. TACC2 depletion enhances ESCC tumorigenesis and progression, as demonstrated in Tacc2 knockout mouse models and by increased growth abilities of ESCC cells. Mechanistically, TACC2 interacts with components of the NuRD and CoREST co-repressor complexes, including MTA1, MBD3, and HMG20B, in the cytoplasm. TACC2 loss leads to the translocation of these proteins into the nucleus, facilitating the formation of functional NuRD and CoREST complexes and the epigenetic repression of CDKN1A. This repression results in elevated CDK1/2 activation. Furthermore, TACC2-deficient cells and ESCC patient-derived organoids with reduced TACC2 expression show increased sensitivity to CDK inhibitors, particularly dinaciclib, which is currently in a phase III trial. Notably, the combination of TACC2-specific RNAi and dinaciclib in subcutaneous ESCC models significantly impairs tumor growth.CONCLUSIONSThe findings suggest a strategy for cancer treatment based on synthetic lethality.FUNDINGFunded by NKRDP, NSFC, GDIIET, GDBABRF, GDECISTP, and SYSUTP.

01 Oct 2024·Molecular Neurobiology

m6A/m1A/m5C-Associated Methylation Alterations and Immune Profile in MDD

Article

Author: Huo, Lijuan ; Fan, Changhe ; Feng, Shujie ; Weng, Xuchu ; Bai, Ayu ; Ren, Xin ; Zhou, Huiying ; Zhou, Ying ; Feng, Zhuxiao ; Ma, Xiaodong

AbstractMajor depressive disorder (MDD) is a prevalent psychiatric condition often accompanied by severe impairments in cognitive and functional capacities. This research was conducted to identify RNA modification-related gene signatures and associated functional pathways in MDD. Differentially expressed RNA modification-related genes in MDD were first identified. And a random forest model was developed and distinct RNA modification patterns were discerned based on signature genes. Then, comprehensive analyses of RNA modification-associated genes in MDD were performed, including functional analyses and immune cell infiltration. The study identified 29 differentially expressed RNA modification-related genes in MDD and two distinct RNA modification patterns. TRMT112, MBD3, NUDT21, and IGF2BP1 of the risk signature were detected. Functional analyses confirmed the involvement of RNA modification in pathways like phosphatidylinositol 3-kinase signaling and nucleotide oligomerization domain (NOD)-like receptor signaling in MDD. NUDT21 displayed a strong positive correlation with type 2 T helper cells, while IGF2BP1 negatively correlated with activated CD8 T cells, central memory CD4 T cells, and natural killer T cells. In summary, further research into the roles of NUDT21 and IGF2BP1 would be valuable for understanding MDD prognosis. The identified RNA modification-related gene signatures and pathways provide insights into MDD molecular etiology and potential diagnostic biomarkers.

01 Apr 2024·Pathology - Research and Practice

Prognostic value of genome-wide methylation in acute-on-chronic hepatitis B liver failure

Article

Author: Wang, Kai ; Fan, Yuchen ; Gao, Shuai ; Xuefei ; Li, Haiming ; Yang, Jieru ; Zhang, Ying

AIMMethylation status of genome varies between pre-acute-on-chronic hepatitis B liver failure (pre-ACHBLF), acute-on-chronic hepatitis B liver failure (ACHBLF), and chronic hepatitis B patients. This study aimed to find better prognostic indicators for acute-on-chronic liver failure.METHODSThe level of global genome methylation in peripheral blood mononuclear cells (PBMCs) was detected. The overall genome methylation rate was determined using MethylFlash™ Methylated DNA Quantification Kit(Colorimetric). DNMT activity were measured using DNA Methyltransferase Activity/Inhibition Assay Kit. Gene expression of DNA methyltransferases (DNMT)，methyl-CpG-binding domain (MBD) were detected by qRT-PCR.RESULTSThe global genome methylation level in ACHBLF group was significantly higher than that in chronic hepatitis B group (P<0.001). There was also obvious difference of the global genome methylation level between pre-ACHBLF group and CHB group (P<0.001). Meanwhile, the activity of DNMT in ACHBLF group was significantly higher than that in chronic hepatitis B group (P<0.001). The mRNA expression level of DNMT1 was higher than that in pre-ACHBLF group (P<0.01) and CHB group (PP<0.001). The mRNA expression level of MBD1 in ACHBLF group was also higher than that in CHB group (P<0.001) and healthy controls (HCs) (P<0.01). And the mRNA expression level of MBD3 and MBD4 in ACHBLF, pre-ACHBLF and CHB group were lower than that in HCs (P<0.001). Meanwhile we observed an opposite change in the mRNA expression level of MECP2. The ROC curve suggested that global genome methylation level was a better prognostic predictor than MELD score in ACHBLF (AUC 0.950, SE 0.0237, 95%CI 0.874-0.986 VS AUC 0.863, SE 0.0439, 95%CI 0.765-0.931, P=0.0429).CONCLUSIONSGenome methylation level can be a good biomarker in predicting the severity and prognosis of ACHBLF.

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MBD3

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