Downregulation of VPS13C Promotes Cisplatin Resistance in Cervical Cancer by Upregulating GSTP1

Overview

Journal iScience

Publisher Cell Press

Date 2023 Jul 31

PMID 37520723

Authors

Xiangyu Tan

Xueqian Wang

Xueyao Liao

Xin Wang

Zhichao Jiang

Wenjia Liang

Chen Cao

Danni Gong

Zheng Hu

Xun Tian

Affiliations

Soon will be listed here.

Abstract

Cisplatin resistance remains a major obstacle limiting the effectiveness of chemotherapy in cervical cancer. However, the underlying mechanism of cisplatin resistance is still unclear. In this study, we demonstrate that vacuolar protein sorting 13 homolog C (VPS13C) deficiency promotes cisplatin resistance in cervical cancer. Moreover, through an RNA sequencing screen, VPS13C deficiency was identified 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 underlying mechanisms of VPS13C in cisplatin resistance and identify VPS13C as a promising candidate for the treatment of chemoresistance in cervical cancer.

Citing Articles

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