WDR82-Mediated H3K4me3 Is Associated with Tumor Proliferation and Therapeutic Efficacy in Pediatric High-Grade Gliomas

Pediatric high-grade gliomas (pHGGs) are common malignant brain tumors without effective treatment and poor patient survival. Abnormal posttranslational modification at the histone H3 tail plays critical roles in tumor cell malignancy. We have previously shown that the trimethylation of lysine 4 at...

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Bibliographic Details
Published in:Cancers 2023-06, Vol.15 (13), p.3429
Main Authors: Wadhwani, Nitin, Nayak, Sonali, Wang, Yufen, Hashizume, Rintaro, Jie, Chunfa, Mania-Farnell, Barbara, James, Charles David, Xi, Guifa, Tomita, Tadanori
Format: Article
Language:English
Subjects:
Biotechnology industry
Brain tumors
Cancer
Chemotherapy
Computer software industry
Epigenetic inheritance
Genes
Gliomas
Instrument industry
Methylene blue
Pediatrics
Post-translational modification
Stem cells
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Summary:Pediatric high-grade gliomas (pHGGs) are common malignant brain tumors without effective treatment and poor patient survival. Abnormal posttranslational modification at the histone H3 tail plays critical roles in tumor cell malignancy. We have previously shown that the trimethylation of lysine 4 at histone H3 (H3K4me3) plays a significant role in pediatric ependymoma malignancy and is associated with tumor therapeutic sensitivity. Here, we show that H3K4me3 and its methyltransferase WDR82 are elevated in pHGGs. A reduction in H3K4me3 by downregulating WDR82 decreases H3K4me3 promoter occupancy and the expression of genes associated with stem cell features, cell proliferation, the cell cycle, and DNA damage repair. A reduction in WDR82-mediated H3K4me3 increases the response of pediatric glioma cells to chemotherapy. These findings suggest that WDR82-mediated H3K4me3 is an important determinant of pediatric glioma malignancy and therapeutic response. This highlights the need for a more thorough understanding of the potential of WDR82 as an epigenetic target to increase therapeutic efficacy and improve the prognosis for children with malignant gliomas.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15133429