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SETD8, a frequently mutated gene in cervical cancer, enhances cisplatin sensitivity by impairing DNA repair

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收录情况： ◇ SCIE

作者：
Wang Xin[1,2] * ; Cao Chen[1] * ; Tan Xiangyu[2] * ; Liao Xueyao[1] * ; Du Xiaofang[1] * ; Wang Xueqian[2] ; Liu Ting[1] ; Gong Danni[1] ; Hu Zheng[3,4,5,6] ; Tian Xun[1,2,7] ;
单位： [1]Department of Obstetrics and Gynecology, Academician Expert Workstation, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, China [2]Department of Gynecological Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China [3]Department of Gynecologic Oncology, Women and Children’s Hospital Affiliated to Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China [4]Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China [5]Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China [6]Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China [7]National Clinical Research Center for Obstetrics and Gynecology,Cancer Biology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China
出处：
DOI： 10.1186/s13578-023-01054-y
ISSN：

关键词： Cisplatin sensitivity SETD8 Cervical cancer DNA repair Whole exome sequencing

摘要：
Cisplatin is commonly used to treat cervical cancer while drug resistance limits its effectiveness. There is an urgent need to identify strategies that increase cisplatin sensitivity and improve the outcomes of chemotherapy.We performed whole exome sequencing (WES) of 156 cervical cancer tissues to assess genomic features related to platinum-based chemoresistance. By using WES, we identified a frequently mutated locus SETD8 (7%), which was associated with drug sensitivity. Cell functional assays, in vivo xenografts tumor growth experiments, and survival analysis were used to investigate the functional significance and mechanism of chemosensitization after SETD8 downregulation. Knockdown of SETD8 increased the responsiveness of cervical cancer cells to cisplatin treatment. The mechanism is exerted by reduced binding of 53BP1 to DNA breaks and inhibition of the non-homologous end joining (NHEJ) repair pathway. In addition, SETD8 expression was positively correlated with resistance to cisplatin and negatively associated with the prognosis of cervical cancer patients. Further, UNC0379 as a small molecule inhibitor of SETD8 was found to enhance cisplatin sensitivity both in vitro and in vivo.SETD8 was a promising therapeutic target to ameliorate cisplatin resistance and improve the efficacy of chemotherapy.© 2023. The Author(s).

基金：
This study was funded by the National Natural Science Foundation of China (grant no. 82172584, 32171465, 82102392, and 81902663); General Program of Natural Science Foundation of Guangdong Province of China (grant no. 2021A1515012438); Guangdong Basic and Applied Basic Research Foundation (grant no. 2020A1515110170); the National Ten Thousand Plan-Young Top Talents of China (grant no. 80000-41180002); application foundation frontier project of Wuhan Science and Technology Bureau (grant no.. 2020020601012324); the Medical Research Project of Wuhan Municipal Health Commission (grant no. WX20Q05, WX21Q09); the Natural Science Foundation of Hubei Province (grant no. 2022CFB133).
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外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
最新[2025]版：
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
JCR分区：
出版当年[2021]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者单位： [1]Department of Obstetrics and Gynecology, Academician Expert Workstation, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, China [2]Department of Gynecological Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Obstetrics and Gynecology, Academician Expert Workstation, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, China [2]Department of Gynecological Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China [3]Department of Gynecologic Oncology, Women and Children’s Hospital Affiliated to Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China [4]Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China [5]Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China [6]Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China [7]National Clinical Research Center for Obstetrics and Gynecology,Cancer Biology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China
推荐引用方式(GB/T 7714)：
Wang Xin,Cao Chen,Tan Xiangyu,et al.SETD8, a frequently mutated gene in cervical cancer, enhances cisplatin sensitivity by impairing DNA repair[J].CELL AND BIOSCIENCE.2023,13(1):doi:10.1186/s13578-023-01054-y.
APA：
Wang Xin,Cao Chen,Tan Xiangyu,Liao Xueyao,Du Xiaofang...&Tian Xun.(2023).SETD8, a frequently mutated gene in cervical cancer, enhances cisplatin sensitivity by impairing DNA repair.CELL AND BIOSCIENCE,13,(1)
MLA：
Wang Xin,et al."SETD8, a frequently mutated gene in cervical cancer, enhances cisplatin sensitivity by impairing DNA repair".CELL AND BIOSCIENCE 13..1(2023)

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