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SETD2 Palmitoylation Mediated by ZDHHC16 in Epidermal Growth Factor Receptor-Mutated Glioblastoma Promotes Ionizing Radiation-Induced DNA Damage

文献类型：期刊论文

作者Fan, Xiaoqing2,3,4,5,6,7; Sun, Suling4,5,6,7; Yang, Haoran3,5,6,7; Ma, Huihui1; Zhao, Chenggang4,5,6,7; Niu, Wanxiang4,5,6,7; Fan, Junqi4,5,6,7; Fang, Zhiyou3,5,6,7; Chen, Xueran3,5,6,7
刊名INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
出版日期2022-07-01
卷号113
ISSN号0360-3016
DOI10.1016/j.ijrobp.2022.02.018
通讯作者Chen, Xueran(xueranchen@cmpt.ac.cn)
英文摘要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. (C) 2022 Elsevier Inc. All rights reserved.
WOS关键词STRAND BREAK REPAIR ; PROTEIN PALMITOYLATION ; HOMOLOGOUS RECOMBINATION ; HETEROGENEITY ; ACTIVATION ; EVOLUTION
资助项目National Natural Science Foundation of China[82172663] ; National Natural Science Foundation of China[82104208] ; National Natural Science Foundation of China[81872066] ; National Natural Science Foundation of China[81773131] ; National Natural Science Foundation of China[81972635] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2018487] ; Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology[2021HSC-CIP011] ; National Key R&D Program of China[2017YFA0503600]
WOS研究方向Oncology ; Radiology, Nuclear Medicine & Medical Imaging
语种英语
出版者ELSEVIER SCIENCE INC
WOS记录号WOS:000833523100025
资助机构National Natural Science Foundation of China ; Youth Innovation Promotion Association of the Chinese Academy of Sciences ; Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; National Key R&D Program of China
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/132155]  
专题中国科学院合肥物质科学研究院
通讯作者Chen, Xueran
作者单位1.Anhui Med Univ, Affiliated Hosp 1, Dept Radiat Oncol, Hefei, Anhui, Peoples R China
2.Univ Sci & Technol China USTC, Affiliated Hosp USTC 1, Dept Anesthesiol, Div Life Sci & Med, Hefei, Anhui, Peoples R China
3.Chinese Acad Sci, Hefei Canc Hosp, Dept Lab Med, Hefei, Anhui, Peoples R China
4.Univ Sci & Technol China, Grad Sch, Sci Isl Branch, Hefei, Anhui, Peoples R China
5.Univ Sci & Technol China, MOE Key Lab Membraneless Organelles & Cellular Dy, Hefei, Anhui, Peoples R China
6.Chinese Acad Sci, Hefei Inst Phys Sci, Inst Hlth & Med Technol, Hefei, Anhui, Peoples R China
7.Chinese Acad Sci, Hefei Inst Phys Sci, Anhui Prov Key Lab Med Phys & Technol, Hefei, Anhui, Peoples R China
推荐引用方式
GB/T 7714		 Fan, Xiaoqing,Sun, Suling,Yang, Haoran,et al. SETD2 Palmitoylation Mediated by ZDHHC16 in Epidermal Growth Factor Receptor-Mutated Glioblastoma Promotes Ionizing Radiation-Induced DNA Damage[J]. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS,2022,113.
APA Fan, Xiaoqing.,Sun, Suling.,Yang, Haoran.,Ma, Huihui.,Zhao, Chenggang.,...&Chen, Xueran.(2022).SETD2 Palmitoylation Mediated by ZDHHC16 in Epidermal Growth Factor Receptor-Mutated Glioblastoma Promotes Ionizing Radiation-Induced DNA Damage.INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS,113.
MLA Fan, Xiaoqing,et al."SETD2 Palmitoylation Mediated by ZDHHC16 in Epidermal Growth Factor Receptor-Mutated Glioblastoma Promotes Ionizing Radiation-Induced DNA Damage".INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 113(2022).

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来源：合肥物质科学研究院

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