Περίληψη:
Glioblastoma (GBM) is the most common primary brain tumor in adults, and the most lethal form of glioma, characterized by variable histopathology, aggressiveness and poor clinical outcome and prognosis. GBMs constitute a challenge for oncologists because of their molecular heterogeneity, extensive invasion, and tendency to relapse. Glioma cells demonstrate a variety of deregulated genomic pathways and extensive interplay with epigenetic alterations. Epigenetic modifications have emerged as essential players in GBM research, with biomarker potential for tumor classification and prognosis and for drug targeting. Histone posttranslational modifications (PTMs) are crucial regulators of chromatin architecture and gene expression, playing a pivotal role in malignant transformation, tumor development and progression. Alteration in the expression of genes coding for lysine and arginine methyltransferases (G9a, SUV39H1 and SETDB1) and acetyltransferases and deacetylases (KAT6A, SIRT2, SIRT7, HDAC4, 6, 9) contribute to GBM pathogenesis. In addition, proteins of the sumoylation pathway are upregulated in GBM cell lines, including E1 (SAE1), E2 (Ubc9) components, and a SUMO-specific protease (SENP1). Preclinical and clinical studies are currently in progress targeting epigenetic enzymes in gliomas, including a new generation of histone deacetylase (HDAC), protein arginine methyltransferase (PRMT) and bromodomain (BRD) inhibitors. Herein, we provide an update on recent advances in glioma epigenetic research, focusing on the role of histone modifications and the use of epigenetic therapy as a valid treatment option for glioblastoma. © 2020 Elsevier Inc.
Συγγραφείς:
Kunadis, E.
Lakiotaki, E.
Korkolopoulou, P.
Piperi, C.
Λέξεις-κλειδιά:
acyltransferase; bromodomain inhibitor; e1 enzyme; e2 enzyme; g9a enzyme; histone; histone deacetylase; histone deacetylase 4; histone deacetylase 6; histone deacetylase 9; kat6a enzyme; protein arginine methyltransferase; senp1 enzyme; setdb1 enzyme; sirtuin 2; sirtuin 7; suv39h1 enzyme; unclassified drug; histone, cancer prognosis; chromatin structure; epigenetics; glioblastoma; histone modification; human; in vitro study; malignant transformation; preclinical study; priority journal; protein expression; protein processing; Review; sumoylation; tumor classification; genetics; glioblastoma; glioma; metabolism; protein processing; tumor recurrence, Glioblastoma; Glioma; Histones; Humans; Neoplasm Recurrence, Local; Protein Processing, Post-Translational
