Cisplatin resistance remains a major obstacle limiting the effectiveness of chemo-therapy in cervical cancer. However, the underlying mechanism of cisplatin resis-tance is still unclear. In this study, we demonstrate that vacuolar protein sorting 13 homolog C (VPS13C) deficiency promotes cisplatin resistance in cervical can-cer. Moreover, through an RNA sequencing screen, VPS13C deficiency was iden-tified as negatively correlated with the high expression of glutathione S-transferase pi gene (GSTP1). Mechanistically, loss of VPS13C contributes to cisplatin resistance by influencing the expression of GSTP1 and inhibiting the downstream c-Jun N-terminal kinase (JNK) pathway. In addition, targeting GSTP1 with the inhibitor NBDHEX effectively rescued the cisplatin resistance induced by VPS13C deficiency. Overall, our findings provide insights into the un-derlying mechanisms of VPS13C in cisplatin resistance and identify VPS13C as a promising candidate for the treatment of chemoresistance in cervical cancer.
基金:
National Natural Science Foundation of China (82172584, 81902663), the
Medical Research Project of Wuhan Municipal Health Commission (WX21Q09), the Natural Science Foundation of Hubei Province (2022CFB133), and the Young Top-notch Talent Cultivation Program of Hubei
Public Health.
第一作者单位:[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Obstet & Gynecol,Wuhan 430030,Hubei,Peoples R China[3]Huazhong Univ Sci & Technol,Natl Clin Res Ctr Obstet & Gynecol,Canc Biol Res Ctr,Key Lab,Minist Educ,Tongji Hosp,Tongji Med Coll,Wuhan 430110,Hubei,Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Obstet & Gynecol,Wuhan 430030,Hubei,Peoples R China[2]Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Obstet & Gynecol,Academician Expert Workstat, Wuhan 430014, Hubei, Peoples R China[3]Huazhong Univ Sci & Technol,Natl Clin Res Ctr Obstet & Gynecol,Canc Biol Res Ctr,Key Lab,Minist Educ,Tongji Hosp,Tongji Med Coll,Wuhan 430110,Hubei,Peoples R China[4]Wuhan Univ, Dept Gynecol Oncol, Zhongnan Hosp, Wuhan 430071, Peoples R China[5]Wuhan Univ, Dept Radiat & Med Oncol, Zhongnan Hosp, Wuhan 430071, Hubei, Peoples R China[6]Wuhan Univ, Hubei Key Lab Tumor Biol Behav, Zhongnan Hosp, Wuhan 430071, Hubei, Peoples R China[7]Wuhan Univ, Hubei Canc Clin Study Ctr, Zhongnan Hosp, Wuhan 430071, Hubei, Peoples R China
推荐引用方式(GB/T 7714):
Tan Xiangyu,Wang Xueqian,Liao Xueyao,et al.Downregulation of VPS13C promotes cisplatin resistance in cervical cancer by upregulating GSTP1[J].ISCIENCE.2023,26(8):doi:10.1016/j.isci.2023.107315.
APA:
Tan, Xiangyu,Wang, Xueqian,Liao, Xueyao,Wang, Xin,Jiang, Zhichao...&Tian, Xun.(2023).Downregulation of VPS13C promotes cisplatin resistance in cervical cancer by upregulating GSTP1.ISCIENCE,26,(8)
MLA:
Tan, Xiangyu,et al."Downregulation of VPS13C promotes cisplatin resistance in cervical cancer by upregulating GSTP1".ISCIENCE 26..8(2023)