机构：[1]Department of Hepatobiliary Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China,临床科室肝胆外科河北医科大学第四医院[2]Department of Emergency, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China,临床科室急诊科河北医科大学第四医院[3]Department of Clinical Laboratory, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China,医技科室检验科河北医科大学第四医院[4]Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200031, China,[5]Pancreatic Cancer Institute, Fudan University, Shanghai 200031, China[6]Hebei Province Key Laboratory of Precision Diagnosis and Therapy for Hepatobiliary-Pancreatic Malignancies, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China河北医科大学第四医院
Ferroptosis is a type of programmed death characterized by iron-dependent lipid peroxidation, and targeting ferroptosis has been shown to efficiently kill highly aggressive cancer cells. Previously, we confirmed that nuclear receptors regulate ferroptosis in pancreatic cancer. However, whether nuclear receptor co-activators regulate ferroptosis is unclear. Here, we show that knocking down the nuclear receptor co-activator, NCOA6, enhances the sensitivity of pancreatic cancer cells to ferroptosis. Mechanistically, NCOA6 knockdown promotes the expression of ACSL4 while inhibiting the expression of SCD1, resulting in changes in lipid metabolism, sensitivity to RSL3-induced ferroptosis, and sensitivity to gemcitabine in pancreatic cancer. The relationships between NCOA6 and ACSL4 or SCD1 are further explored in clinical specimens. This study reveals that targeting NCOA6 might alleviate gemcitabine resistance in pancreatic cancer.
基金：
This work was supported by the grants from the Medical Science
Research Project of Hebei (No. 20230884), the Hebei Natural
Science Foundation (No. H2022206335) and the National Natural
Science Foundation of China (No. 82173281).
语种：
外文
PubmedID：
中科院分区：
出版当年[2025]版：
大类|2 区生物学
小类|2 区生化与分子生物学2 区生物物理
最新[2025]版：
大类|2 区生物学
小类|2 区生化与分子生物学2 区生物物理
第一作者：
第一作者机构：[1]Department of Hepatobiliary Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China,[6]Hebei Province Key Laboratory of Precision Diagnosis and Therapy for Hepatobiliary-Pancreatic Malignancies, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Hepatobiliary Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China,[4]Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200031, China,[5]Pancreatic Cancer Institute, Fudan University, Shanghai 200031, China[6]Hebei Province Key Laboratory of Precision Diagnosis and Therapy for Hepatobiliary-Pancreatic Malignancies, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
推荐引用方式(GB/T 7714)：
Jia Yuming,Ye Zeng,Wang Xin,et al.NCOA6 knockdown enhances RSL3-induced ferroptosis in pancreatic cancer cells and increases the sensitivity to gemcitabine[J].Acta Biochimica Et Biophysica Sinica.2025,doi:10.3724/abbs.2024221.
APA：
Jia Yuming,Ye Zeng,Wang Xin,Deng Yanli,Wang Chao...&Peng Li.(2025).NCOA6 knockdown enhances RSL3-induced ferroptosis in pancreatic cancer cells and increases the sensitivity to gemcitabine.Acta Biochimica Et Biophysica Sinica,,
MLA：
Jia Yuming,et al."NCOA6 knockdown enhances RSL3-induced ferroptosis in pancreatic cancer cells and increases the sensitivity to gemcitabine".Acta Biochimica Et Biophysica Sinica .(2025)
