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Genome-Wide CRISPR-Cas9 Screening Identifies NF-κB/E2F6 Responsible for EGFRvIII-Associated Temozolomide Resistance in Glioblastoma

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资源类型：

收录情况： ◇ SCIE ◇ EI

作者：
Kai Huang[1,2] * ; Xing Liu[3] * ; Yansheng Li[1,2] * ; Qixue Wang[1,2] ; Junhu Zhou[1,2] ; Yunfei Wang[1,2] ; Feng Dong[4] ; Chao Yang[1,2] ; Zhiyan Sun[3] ; Chuan Fang[5] ; Chaoyong Liu[1,2] ; Yanli Tan[6] ; Xudong Wu[4] ; Tao Jiang[3] ; Chunsheng Kang[1,2] ;
机构： [1]Tianjin Neurological Institute Key Laboratory of Post-Neurotrauma Neuro-Repair and Regeneration in Central Nervous System Ministry of Education and Tianjin City Tianjin 300052, China [2]Department of Neurosurgery Tianjin Medical University General Hospital Tianjin 300052, China [3]Beijing Neurosurgical Institute Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050, China [4]Department of Cell Biology 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics Tianjin Key Laboratory of Medical Epigenetics Tianjin Medical University Tianjin 300070, China [5]Department of Neurosurgery Affiliated Hospital of Hebei University Baoding 071000, China [6]Department of Pathology Affiliated Hospital of Hebei University Baoding 071000, China
出处：
DOI： 10.1002/advs.201900782
ISSN：

关键词： CRISPR-Cas9 libraries E2F6 glioblastoma (GBM) temozolomide (TMZ) resistance

摘要：
Amplification of epidermal growth factor receptor (EGFR) and active mutant EGFRvIII occurs frequently in glioblastoma (GBM) and contributes to chemo/radio-resistance in various cancers, especially in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in GBM could benefit cancer patients. A genome-wide screening under a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 library is conducted to identify the genes that confer resistance to TMZ in EGFRvIII-expressing GBM cells. Deep sgRNA sequencing reveals 191 candidate genes that are responsible for TMZ resistance in EGFRvIII-expressing GBM cells. Notably, E2F6 is proven to drive a TMZ resistance, and E2F6 expression is controlled by the EGFRvIII/AKT/NF-κB pathway. Furthermore, E2F6 is shown as a promising therapeutic target for TMZ resistance in orthotopic GBM cell line xenografts and GBM patient-derived xenografts models. After integrating clinical data with paired primary–recurrent RNA sequencing data from 134 GBM patients who received TMZ treatment after surgery, it has been revealed that the E2F6 expression level is a predictive marker for TMZ response. Therefore, the inhibition of E2F6 is a promising strategy to conquer TMZ resistance in GBM. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

基金：
This work was supported by the National Natural Science Foundation of China (Grant No. 81772667), the Beijing Tianjin Hebei basic research cooperation project (Grant nos. 18JCZDJC45500 and H2018201306), the Hebei Province technical innovation guidance funded projects of China (Grant No. 18247792D) and the Tianjin Municipal Science and Technology Commission Project (15ZXLCSY00060, 15ZXJZSY00040).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类 | 1 区 工程技术
小类 | 2 区 化学综合 2 区 材料科学：综合 2 区 纳米科技
最新[2023]版：
大类 | 1 区 材料科学
小类 | 1 区 化学：综合 1 区 材料科学：综合 2 区 纳米科技
JCR分区：
出版当年[2017]版：
Q1 NANOSCIENCE & NANOTECHNOLOGY Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
最新[2023]版：
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2017版] 出版当年五年平均 出版前一年[2016版] 出版后一年[2018版]

第一作者：
第一作者机构： [1]Tianjin Neurological Institute Key Laboratory of Post-Neurotrauma Neuro-Repair and Regeneration in Central Nervous System Ministry of Education and Tianjin City Tianjin 300052, China [2]Department of Neurosurgery Tianjin Medical University General Hospital Tianjin 300052, China
共同第一作者：
通讯作者：
通讯机构： [1]Tianjin Neurological Institute Key Laboratory of Post-Neurotrauma Neuro-Repair and Regeneration in Central Nervous System Ministry of Education and Tianjin City Tianjin 300052, China [2]Department of Neurosurgery Tianjin Medical University General Hospital Tianjin 300052, China [3]Beijing Neurosurgical Institute Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050, China [4]Department of Cell Biology 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics Tianjin Key Laboratory of Medical Epigenetics Tianjin Medical University Tianjin 300070, China
推荐引用方式(GB/T 7714)：
Kai Huang,Xing Liu,Yansheng Li,et al.Genome-Wide CRISPR-Cas9 Screening Identifies NF-κB/E2F6 Responsible for EGFRvIII-Associated Temozolomide Resistance in Glioblastoma[J].ADVANCED SCIENCE.2019,6(17):1900782.doi:10.1002/advs.201900782.
APA：
Kai Huang,Xing Liu,Yansheng Li,Qixue Wang,Junhu Zhou...&Chunsheng Kang.(2019).Genome-Wide CRISPR-Cas9 Screening Identifies NF-κB/E2F6 Responsible for EGFRvIII-Associated Temozolomide Resistance in Glioblastoma.ADVANCED SCIENCE,6,(17)
MLA：
Kai Huang,et al."Genome-Wide CRISPR-Cas9 Screening Identifies NF-κB/E2F6 Responsible for EGFRvIII-Associated Temozolomide Resistance in Glioblastoma".ADVANCED SCIENCE 6..17(2019):1900782

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