Genome-wide CRISPR/Cas9 screening identifies CARHSP1 responsible for radiation resistance in glioblastoma

作者全名："Zhu, Guo-dong; Yu, Jing; Sun, Zheng-yu; Chen, Yan; Zheng, Hong-mei; Lin, Mei-lan; Shi Ou-yang; Liu, Guo-long; Zhang, Jie-wen; Shao, Feng-min"

作者地址："[Zhu, Guo-dong] Guangzhou Geriatr Hosp, Dept Geriatr, Guangzhou 510180, Peoples R China; [Zhu, Guo-dong; Lin, Mei-lan; Liu, Guo-long] South China Univ Technol, Guangzhou Peoples Hosp 1, Sch Med, Dept Geriatr, Guangzhou 510180, Peoples R China; [Zhu, Guo-dong; Lin, Mei-lan; Liu, Guo-long] South China Univ Technol, Guangzhou Peoples Hosp 1, Sch Med, Dept Oncol, Guangzhou 510180, Peoples R China; [Yu, Jing] Huazhong Univ Sci & Technol, Dept Blood Transfus, Wuhan Hosp 1, Wuhan Hosp Tradit Chinese & Western Med,Tongji Me, Wuhan 430022, Peoples R China; [Sun, Zheng-yu; Zhang, Jie-wen] Zhengzhou Univ, Henan Prov Peoples Hosp, Dept Neurol, Peoples Hosp, Zhengzhou 450003, Henan, Peoples R China; [Chen, Yan] Chongqing Med Univ, Dept Geriatr, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Zheng, Hong-mei] Huazhong Univ Sci & Technol, Hubei Canc Hosp, Tongji Med Coll, Dept Breast Surg, Wuhan 430079, Peoples R China; [Zheng, Hong-mei] Hubei Prov Clin Res Ctr Breast Canc, Wuhan 430079, Peoples R China; [Shi Ou-yang] Guangzhou Med Univ, Dept Infect Dis, Affiliated Hosp 5, Guangzhou 510150, Peoples R China; [Shao, Feng-min] Zhengzhou Univ, Henan Prov Peoples Hosp, Dept Nephrol, Henan Prov Key Lab Kidney Dis & Immunol,Peoples H, Zhengzhou 450003, Henan, Peoples R China"

通信作者："Zhang, JW (corresponding author), Zhengzhou Univ, Henan Prov Peoples Hosp, Dept Neurol, Peoples Hosp, Zhengzhou 450003, Henan, Peoples R China.; Shao, FM (corresponding author), Zhengzhou Univ, Henan Prov Peoples Hosp, Dept Nephrol, Henan Prov Key Lab Kidney Dis & Immunol,Peoples H, Zhengzhou 450003, Henan, Peoples R China."

来源：CELL DEATH & DISEASE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000677604400001

JCR分区：Q1

影响因子：9

年份：2021

卷号：12

期号：8

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Glioblastomas (GBM) is the most common primary malignant brain tumor, and radiotherapy plays a critical role in its therapeutic management. Unfortunately, the development of radioresistance is universal. Here, we identified calcium-regulated heat-stable protein 1 (CARHSP1) as a critical driver for radioresistance utilizing genome-wide CRISPR activation screening. This is a protein with a cold-shock domain (CSD)-containing that is highly similar to cold-shock proteins. CARHSP1 mRNA level was upregulated in irradiation-resistant GBM cells and knockdown of CARHSP1 sensitized GBM cells to radiotherapy. The high expression of CARHSP1 upon radiation might mediate radioresistance by activating the inflammatory signaling pathway. More importantly, patients with high levels of CARHSP1 had poorer survival when treated with radiotherapy. Collectively, our findings suggested that targeting the CARHSP1/TNF-alpha inflammatory signaling activation induced by radiotherapy might directly affect radioresistance and present an attractive therapeutic target for GBM, particularly for patients with high levels of CARHSP1."

基金机构："Guangdong Planned Project of Science and Technology [2014A020221001]; Guangzhou Planned Project of Science and Technology [202102010030, 201704020105]"

基金资助正文："This work was supported by grants from Guangdong Planned Project of Science and Technology (2014A020221001), Guangzhou Planned Project of Science and Technology (202102010030, 201704020105)."