Histone Methyltransferases G9a/Ehmt2 and GLP/Ehmt1 Are Associated with Cell Viability and Poorer Prognosis in Neuroblastoma and Ewing Sarcoma

Changes in epigenetic programming have been proposed as being key events in the initiation and progression of childhood cancers. HMT euchromatic histone lysine methyltransferase 2 (G9a, EHMT2), which is encoded by the G9a (Ehmt2) gene, as well as its related protein GLP, which is encoded by the GLP/...

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Published in:International journal of molecular sciences 2023-10, Vol.24 (20), p.15242
Main Authors: Souza, Barbara Kunzler, Freire, Natalia Hogetop, Monteiro, Thiago Santos, Herlinger, Alice Laschuk, Jaeger, Mariane, Dalmolin, Matheus G. S., de Farias, Caroline Brunetto, Gregianin, Lauro, Brunetto, André T., Brunetto, Algemir L., Thiele, Carol J., Roesler, Rafael
Format: Article
Language:English
Subjects:
Biomarkers
Cells
Disease
Epigenetics
Ewing sarcoma
Ewings sarcoma
Fibroblasts
G9a
GLP
histone methyltransferase
Medical prognosis
Metastasis
Neuroblastoma
pediatric cancer
Pediatrics
Proteins
Tumors
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Summary:Changes in epigenetic programming have been proposed as being key events in the initiation and progression of childhood cancers. HMT euchromatic histone lysine methyltransferase 2 (G9a, EHMT2), which is encoded by the G9a (Ehmt2) gene, as well as its related protein GLP, which is encoded by the GLP/Ehmt1 gene, participate in epigenetic regulation by contributing to a transcriptionally repressed chromatin state. G9a/GLP activation has been reported in several cancer types. Herein, we evaluated the role of G9a in two solid pediatric tumors: neuroblastoma (NB) and Ewing sarcoma (ES). Our results show that G9a/Ehmt2 and GLP/Ehmt1 expression is higher in tumors with poorer prognosis, including St4 International Neuroblastoma Staging System (INSS) stage, MYCN amplified NB, and metastatic ES. Importantly, higher G9a and GLP levels were associated with shorter patient overall survival (OS) in both NB and ES. Moreover, pharmacological inhibition of G9a/GLP reduced cell viability in NB and ES cells. These findings suggest that G9a and GLP are associated with more aggressive NB and ES tumors and should be further investigated as being epigenetic targets in pediatric solid cancers.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms242015242