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Downregulation of VPS13C promotes cisplatin resistance in cervical cancer by upregulating GSTP1

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单位: [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
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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.

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大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
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大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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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
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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
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