Carnitine palmitoyltransferase 1C promotes EMT-associated cisplatin resistance in non-small cell lung cancer cells  

作　　者：Renjie Chen Jiahui Wang Shuoyu Huang Xuefeng Hu Xinran He Tiange Zhang Yunhan Hu Huijun Wei Sihui Nian Yushu Huang Zhihao Wu 

机构地区：[1]Research Laboratory of Tumor Microenvironment,Wannan Medical College,Wuhu 241001,China [2]School of Laboratory Medicine,Wannan Medical College,Wuhu 241001,China [3]School of Anesthesiology,Wannan Medical College,Wuhu 241001,China [4]School of Medical Imageology,Wannan Medical College,Wuhu 241001,China [5]School of Clinical Medicine,Wannan Medical College,Wuhu 241001,China [6]Anhui Province Key Laboratory of Active Biological Macro-molecules Research,Wannan Medical College,Wuhu 241001,China [7]Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui,Wannan Medical College,Wuhu 241001,China [8]School of Pharmacy,Wannan Medical College,Wuhu 241001,China [9]Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation,Wannan Medical College,Wuhu 241001,China [10]Anhui Provincial Engineering Research Center for Dental Materials and Application,Wannan Medical College,Wuhu 241001,China

出　　处：《Cancer Biology & Medicine》2025年第1期48-66,共19页癌症生物学与医学(英文版)

基　　金：supported by the National Natural Science Foundation of China(Grant No.81872371);the Open Project Program of State Key Laboratory of Molecular Oncology(Grant No.SKL-KF-2019-11);the Program for Excellent Sci-tech Innovation Teams of Universities in Anhui Province(Grant No.2023AH010073);the Provincial-level Quality Project in Higher Education Institutions of Anhui Province(Grant No.2022jyxm1710);the College Students Innovation and Entrepreneurship Training Program(Grant No.S202310368028 and S202410368035);the Health Science Research Project of Anhui Province(Grant No.AHWJ2022a028)。

摘　　要：Objective:Lung cancer is the most common cause of cancer-related deaths worldwide.Platinum-based chemotherapy is one of the main treatment options for patients with non-small cell lung cancer(NSCLC)but the effectiveness of chemotherapy is encumbered by drug resistance.Therefore,understanding the molecular mechanisms underlying chemotherapy resistance is crucial in improving treatment outcomes and prognosis.Methods:The cell viability assay and apoptosis were used to analyze chemoresistance.Western blot analysis and wound healing testing were used to evaluate the epithelial-to-mesenchymal transition(EMT).Immunoprecipitation was used for analysis of protein modification.Promoter activity was determined using the luciferase reporter assay.Immunofluorescence staining was used to determine reactive oxygen species levels.The expression patterns of EMT markers and carnitine palmitoyltransferase 1C(CPT1C)were determined by Western blot analysis.Results:CPT1C,which was shown to be highly expressed in lung cancer,is associated with cisplatin resistance in NSCLC cells.CPT1C depletion increased NSCLC cell sensitivity to cisplatin,while overexpression of CPT1C increased NSCLC cell resistance to cisplatin.Induction of EMT mediated CPT1C-induced cisplatin resistance.Ectopic expression of Snail reversed the increase in cisplatin sensitivity triggered by CPT1C knockdown.Moreover,CPT1C was shown to be regulated at the post-translational level and an E3-ubiquitin ligase,NEDD4L,was shown to be a major regulator of CPT1C stability and activity.Conclusions:These data provide evidence for the first time that the lipid metabolism enzyme,CPT1C,mediates resistance to chemotherapy.Therefore,the use of combination therapy with a CPT1C inhibitor may be a promising new avenue in lung cancer treatment.

关 键 词：CPT1C CHEMORESISTANCE EMT NEDD4L NSCLC 

分 类 号：R734.2[医药卫生—肿瘤]