The Role of ZEB2 Expression in Pediatric and Adult Glioblastomas

Myung, Jae Kyung; Choi, Seung Ah; Kim, Seung Ki; Kim, Seong Ik; Park, Jin Woo; Park, Shin Young

doi:10.21873/anticanres.14763

Cited by 4 publications

(3 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, OLIG2 is an upstream activator of ZEB2 and increased OLIG2 levels have been shown to activate ZEB2 during development leading to oligodendrocyte precursor cell (OPC) maturation and myelination [67]. ZEB2 is an established regulator of EMT and has been linked to increased invasiveness and migration, poor prognosis for glioma patients, and is upregulated in glioblastoma and in DIPG as demonstrated in this study [36,37,68]. Interestingly, ZEB2 is also linked to Notch signaling during Schwann cell development and acts as a repressor of Notch-Hey2 signaling [69].…”

Section: Discussionmentioning

confidence: 66%

“…This finding was further supported via H3K4me3 chromatin immunoprecipitation (ChIP) qPCR of two such regions. COBL is an actin nucleator involved in neurite outgrowth and of particular importance to proper cerebellum formation [34,35] and ZEB2 is a zinc finger E-box binding transcription factor that plays a role in promoting migration and invasion of both adult and pediatric glioblastoma cells [36,37]. We demonstrated a significant decrease in H3K4me3 levels upon reversion to wild-type in promoter regions of both genes (Fig.…”

Section: K27m-dependent Accessible Chromatin Regions In Pediatric Gli...mentioning

confidence: 70%

See 1 more Smart Citation

Histone H3.3 K27M chromatin functions implicate a network of neurodevelopmental factors including ASCL1 and NEUROD1 in DIPG

Lewis

Klein

Kelly

et al. 2022

Epigenetics & Chromatin

View full text Add to dashboard Cite

Background The histone variant H3.3 K27M mutation is a defining characteristic of diffuse intrinsic pontine glioma (DIPG)/diffuse midline glioma (DMG). This histone mutation is responsible for major alterations to histone H3 post-translational modification (PTMs) and subsequent aberrant gene expression. However, much less is known about the effect this mutation has on chromatin structure and function, including open versus closed chromatin regions as well as their transcriptomic consequences. Results Recently, we developed isogenic CRISPR-edited DIPG cell lines that are wild-type for histone H3.3 that can be compared to their matched K27M lines. Here we show via ATAC-seq analysis that H3.3K27M glioma cells have unique accessible chromatin at regions corresponding to neurogenesis, NOTCH, and neuronal development pathways and associated genes that are overexpressed in H3.3K27M compared to our isogenic wild-type cell line. As to mechanisms, accessible enhancers and super-enhancers corresponding to increased gene expression in H3.3K27M cells were also mapped to genes involved in neurogenesis and NOTCH signaling, suggesting that these pathways are key to DIPG tumor maintenance. Motif analysis implicates specific transcription factors as central to the neuro-oncogenic K27M signaling pathway, in particular, ASCL1 and NEUROD1. Conclusions Altogether our findings indicate that H3.3K27M causes chromatin to take on a more accessible configuration at key regulatory regions for NOTCH and neurogenesis genes resulting in increased oncogenic gene expression, which is at least partially reversible upon editing K27M back to wild-type.

show abstract

Section: Discussionmentioning

confidence: 66%

Section: K27m-dependent Accessible Chromatin Regions In Pediatric Gli...mentioning

confidence: 70%

Histone H3.3 K27M chromatin functions implicate a network of neurodevelopmental factors including ASCL1 and NEUROD1 in DIPG

Lewis

Klein

Kelly

et al. 2022

Epigenetics & Chromatin

View full text Add to dashboard Cite

show abstract

“…The expression of IDH1 R132H, p53, EGFR and Ki67 in formalin-xed para n embedded (FFPE) tumor tissues was analysed by standard immunohistochemistry technique carried out in the Department of Neuropathology of our University Hospital [23]. The following antibody were used: anti-p53 (DO-7, 1:40; Cell Marque, Hot Springs, AZ, USA), which detect both wild type and mutant p53 protein [24]; anti-IDH1 R132H (DIA-H09, 1:50; Dianova, Hamburg, Germany); anti-EGFR (clone H11; 1:200; Dako, Glostrup, Denmark); anti Ki-67 (MIB-1, 1:50; Dako, Glostrup, Denmark) [23]. Following counterstaining with hematoxylin, slides were dehydrated, mounted and observed under light microscope.…”

Section: Clinical and Pathological Analysismentioning

confidence: 99%

MEX3A is a new diagnostic, independent prognostic biomarker and a promising therapeutic target in gliomas

Bufalieri,

Armocida,

Cucinotta

et al. 2024

Preprint

View full text Add to dashboard Cite

Gliomas are the most common malignant brain tumors with a dismal prognosis. Despite the progress in defining molecular features, no therapies targeting the known biomarkers significantly increase the survival rate of glioma patients. Recently, it has been demonstrated that high expression of Muscle Excess 3A (MEX3A) in gliomas correlates with poor overall survival (OS), yet its clinical significance remains largely unknown. In this study, we assessed the correlation between the expression of MEX3A and clinical and molecular characteristics of a cohort of 71 glioma patients, determining its diagnostic and prognostic value and exploring its potential as an innovative therapeutic target. Our analysis revealed that elevated MEX3A expression associates with more severe clinicopathological and molecular features of glioma patients. Furthermore, MEX3A exhibits high diagnostic accuracy and correlates with poor OS and progression free survival. Multivariate COX regression analysis also identified high MEX3A expression as an independent prognostic factor for OS. Notably, MEX3A genetic depletion inhibits primary human glioma cells growth both in vitro and in vivo. Our finding emphasizes the connection between MEX3A expression and clinical and molecular aspects in glioma patients, indicating that MEX3A expression represents a new diagnostic and independent prognostic biomarker, as well as a promising therapeutic target.

show abstract

miR-637 Prevents Glioblastoma Progression by Interrupting ZEB2/WNT/β-catenin Cascades

et al. 2021

View full text Add to dashboard Cite

Glioblastomas (GBMs) are the most frequent primary malignancies in the central nervous system. Aberrant activation of WNT/β-catenin signaling pathways is critical for GBM malignancy. However, the regulation of WNT/β-catenin signaling cascades remains unclear. Presently, we observed the increased expression of ZEB2 and decreased expression of miR-637 in GBM. The expression of miR-637 was negatively correlated with expression of ZEB2. miR-637 overexpression overcame the ZEB2-enhanced cell proliferation and G1/S phase transition. In addition, miR-637 suppressed canonical WNT/β-catenin pathways by targeting WNT7A directly. Gain-and loss-of-function experiments in U251 mice demonstrated that miR-637 inhibited cell proliferation and arrested the G1/S phase transition, leading to tumor growth suppression. The collective ndings suggest that ZEB2 and WNT/β-catenin cascades merge at miR-637 and the ectopic expression of miR-637 disturbs ZEB2/WNT/β-Catenin-mediated GBM growth. The ndings should inform improved β-catenin-targeted therapy against GBM.

show abstract

The Role of ZEB2 Expression in Pediatric and Adult Glioblastomas

Cited by 4 publications

References 31 publications

Histone H3.3 K27M chromatin functions implicate a network of neurodevelopmental factors including ASCL1 and NEUROD1 in DIPG

Histone H3.3 K27M chromatin functions implicate a network of neurodevelopmental factors including ASCL1 and NEUROD1 in DIPG

MEX3A is a new diagnostic, independent prognostic biomarker and a promising therapeutic target in gliomas

miR-637 Prevents Glioblastoma Progression by Interrupting ZEB2/WNT/β-catenin Cascades

Contact Info

Product

Resources

About