2026-10-12T23:23:40Z https://www.scidb.cn/oai

10.57760/sciencedb.11065 2023-09-11T14:12:26Z

2023-09-11 SETD2 Palmitoylation Mediated by ZDHHC16 in Epidermal Growth Factor Receptor-Mutated Glioblastoma Promotes Ionizing Radiation-Induced DNA Damage doi:10.57760/sciencedb.11065 en Purpose: The prevalence of epidermal growth factor receptor (EGFR) mutations in glioblastoma multiforme (GBM) has elicited a significant focus on EGFR as a potential drug target. However, no significant clinical advancement in GBM treatment has occurred.Methods and materials: Bioinformatics analysis, western blotting, immunofluorescence, and immunohistochemistry were performed to detect the expression of ZDHHC16 and genetic EGFR alterations in GBM. The biological function of ZDHHC16/SETD2/H3K36me3 signaling axis after EGFR alterations was demonstrated by various in vitro (pharmacologic treatment, flow cytometry, transwell migration assay, and coimmunoprecipitation) and in vivo (xenograft model) experiments.Results: We demonstrate that the ZDHHC16/SETD2/H3K36me3 signaling axis was inactivated in EGFR-altered GBM. ZDHHC16 was downregulated in GBM versus normal brain tissue; this was significantly related to EGFR alterations. These events contributed to p53 activation, halting cells at the G1/S checkpoint. Furthermore, DNA damage repair signaling in EGFR-amplified GBMs was affected after ionizing radiation-induced DNA damage via reduced SETD2 palmitoylation and methylation of its target, H3K36. Our findings suggest that a depalmitoylation inhibitor, PalmB, is useful as a potentially novel adjuvant treatment for patients with GBM undergoing radiation therapy.Conclusions: Our data present novel mechanistic evidence relating to signaling pathways with DNA damage responses in EGFR-mutated GBM. ZDHHC16; SETD2; H3K36me3; EGFR; DNA damage repair; ionizing radiation; glioblastoma multiforme Fan Xiaoqing Sun Suling Yang Haoran Chen Xueran PUBLIC https://creativecommons.org/licenses/by/4.0/ dataset http://www.doi.org/10.1016/j.ijrobp.2022.02.018 Science Data Bank