Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

EHMT2/G9a as an Epigenetic Target in Pediatric and Adult Brain Tumors

Version 1 : Received: 13 August 2021 / Approved: 16 August 2021 / Online: 16 August 2021 (12:31:31 CEST)

How to cite: Souza, B.K.; Freire, N.H.; Jaeger, M.; de Farias, C.B.; Brunetto, A.L.; Brunetto, A.T.; Roesler, R. EHMT2/G9a as an Epigenetic Target in Pediatric and Adult Brain Tumors. Preprints 2021, 2021080335 (doi: 10.20944/preprints202108.0335.v1). Souza, B.K.; Freire, N.H.; Jaeger, M.; de Farias, C.B.; Brunetto, A.L.; Brunetto, A.T.; Roesler, R. EHMT2/G9a as an Epigenetic Target in Pediatric and Adult Brain Tumors. Preprints 2021, 2021080335 (doi: 10.20944/preprints202108.0335.v1).

Abstract

Epigenetic mechanisms, including post-translational modifications of DNA and histones that influence chromatin structure, regulate gene expression during normal development, and are also involved in carcinogenesis and cancer progression. The histone methyltransferase G9a (euchromatic histone lysine methyltransferase 2, EHMT2), which mostly mediates mono- and dimethylation by histone H3 lysine 9 (H3K9), influences gene expression involved in embryonic development and tissue differentiation. Overexpression of G9a has been observed in several cancer types, and different classes of G9a inhibitors have been developed as potential anticancer agents. Here, we review the emerging evidence suggesting the involvement of changes in G9a activity in brain tumors, namely glioblastoma (GBM), the main type of primary malignant brain cancer in adults, and medulloblastoma (MB), the most common type of malignant brain cancer in children. We also dis cuss the role of G9a in neuroblastoma (NB) and the drug development of G9a inhibitors. Finally, we present evidence that G9a inhibition dose-dependently reduces MB cell viability, and that transcriptional levels of G9a are higher in MB tumors belonging to the SHH, Group 3, and Group 4, compared to Wnt tumors. Importantly, our findings suggest that higher G9a gene expression may be a predictor of poor prognosis in patients with SHH MB.

Keywords

G9a; EHMT2; glioblastoma; medulloblastoma; epigenetics; brain tumor

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