ZNF263/CPT1B轴调节脂肪酸β-氧化,从而影响肺腺癌的顺铂耐药性。

IF 2.9 3区 医学 Q2 GENETICS & HEREDITY Pharmacogenomics Journal Pub Date : 2024-11-05 DOI:10.1038/s41397-024-00355-w
Renhe Yan, Caibin Zheng, Suting Qian, Kezhi Li, Xiangsheng Kong, Shunhang Liao
{"title":"ZNF263/CPT1B轴调节脂肪酸β-氧化,从而影响肺腺癌的顺铂耐药性。","authors":"Renhe Yan, Caibin Zheng, Suting Qian, Kezhi Li, Xiangsheng Kong, Shunhang Liao","doi":"10.1038/s41397-024-00355-w","DOIUrl":null,"url":null,"abstract":"<p><p>Cisplatin is widely used as a conventional chemotherapy drug for lung adenocarcinoma (LUAD) patients. However, the chemical resistance greatly limits its therapeutic potential. The study aimed to uncover the specific role and new mechanisms of CPT1B in the cisplatin resistance of LUAD. Bioinformatics analysis was utilized to analyze the expression level and enriched pathway of CPT1B in LUAD. The expression of CPT1B in LUAD cells was determined by utilizing quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB). The cisplatin resistance in LUAD was measured with IC<sub>50</sub> values obtained from the CCK-8 assay. We used the corresponding reagent kit and WB analysis to determine the levels of triglycerides, cholesterol, phospholipids, fatty acid β-oxidation (FAO) rate, and expression of lipid metabolism-related proteins. Finally, the regulation relationship between CPT1B and ZNF263 was confirmed through bioinformatics analysis, dual-luciferase, and chromatin immunoprecipitation assays. The present investigation revealed that CPT1B was upregulated in LUAD, participating in fatty acid metabolism pathways. In vitro studies have shown that upregulation of CPT1B promoted cisplatin resistance in LUAD cells. This promotion effect induced by the high expression of CPT1B on cisplatin resistance in LUAD was weakened after the addition of the FAO inhibitor Etomoxir. Mechanistically, ZNF263 was capable of binding to the promoter of CPT1B to activate its transcription, thereby enhancing FAO and promoting cisplatin resistance in LUAD cells. In summary, ZNF263 enhances cisplatin resistance in LUAD cells by upregulating CPT1B expression. This study enriches the molecular mechanisms of LUAD chemotherapy resistance and provides new directions for exploring therapeutic targets for LUAD.</p>","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 6","pages":"33"},"PeriodicalIF":2.9000,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The ZNF263/CPT1B axis regulates fatty acid β-oxidation to affect cisplatin resistance in lung adenocarcinoma.\",\"authors\":\"Renhe Yan, Caibin Zheng, Suting Qian, Kezhi Li, Xiangsheng Kong, Shunhang Liao\",\"doi\":\"10.1038/s41397-024-00355-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cisplatin is widely used as a conventional chemotherapy drug for lung adenocarcinoma (LUAD) patients. However, the chemical resistance greatly limits its therapeutic potential. The study aimed to uncover the specific role and new mechanisms of CPT1B in the cisplatin resistance of LUAD. Bioinformatics analysis was utilized to analyze the expression level and enriched pathway of CPT1B in LUAD. The expression of CPT1B in LUAD cells was determined by utilizing quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB). The cisplatin resistance in LUAD was measured with IC<sub>50</sub> values obtained from the CCK-8 assay. We used the corresponding reagent kit and WB analysis to determine the levels of triglycerides, cholesterol, phospholipids, fatty acid β-oxidation (FAO) rate, and expression of lipid metabolism-related proteins. Finally, the regulation relationship between CPT1B and ZNF263 was confirmed through bioinformatics analysis, dual-luciferase, and chromatin immunoprecipitation assays. The present investigation revealed that CPT1B was upregulated in LUAD, participating in fatty acid metabolism pathways. In vitro studies have shown that upregulation of CPT1B promoted cisplatin resistance in LUAD cells. This promotion effect induced by the high expression of CPT1B on cisplatin resistance in LUAD was weakened after the addition of the FAO inhibitor Etomoxir. Mechanistically, ZNF263 was capable of binding to the promoter of CPT1B to activate its transcription, thereby enhancing FAO and promoting cisplatin resistance in LUAD cells. In summary, ZNF263 enhances cisplatin resistance in LUAD cells by upregulating CPT1B expression. This study enriches the molecular mechanisms of LUAD chemotherapy resistance and provides new directions for exploring therapeutic targets for LUAD.</p>\",\"PeriodicalId\":54624,\"journal\":{\"name\":\"Pharmacogenomics Journal\",\"volume\":\"24 6\",\"pages\":\"33\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-11-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacogenomics Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41397-024-00355-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenomics Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41397-024-00355-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

摘要

顺铂被广泛用作肺腺癌(LUAD)患者的常规化疗药物。然而,耐药性极大地限制了其治疗潜力。本研究旨在揭示 CPT1B 在 LUAD 顺铂耐药性中的特殊作用和新机制。该研究利用生物信息学分析方法分析了CPT1B在LUAD中的表达水平和富集途径。利用定量反转录聚合酶链反应(qRT-PCR)和免疫印迹(WB)测定了CPT1B在LUAD细胞中的表达。LUAD的顺铂耐药性是通过CCK-8检测法获得的IC50值测定的。我们使用相应的试剂盒和 WB 分析测定了甘油三酯、胆固醇、磷脂、脂肪酸 β-氧化(FAO)率和脂代谢相关蛋白的表达水平。最后,通过生物信息学分析、双荧光素酶和染色质免疫沉淀实验证实了 CPT1B 和 ZNF263 之间的调控关系。本研究发现,CPT1B在LUAD中上调,参与脂肪酸代谢途径。体外研究表明,CPT1B的上调促进了LUAD细胞对顺铂的耐药性。在加入FAO抑制剂Etomoxir后,CPT1B的高表达对LUAD顺铂耐药性的促进作用减弱。从机制上看,ZNF263能够与CPT1B的启动子结合,激活其转录,从而增强FAO,促进LUAD细胞对顺铂的耐药性。综上所述,ZNF263通过上调CPT1B的表达增强了LUAD细胞的顺铂耐药性。这项研究丰富了LUAD化疗耐药的分子机制,为探索LUAD的治疗靶点提供了新的方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
The ZNF263/CPT1B axis regulates fatty acid β-oxidation to affect cisplatin resistance in lung adenocarcinoma.

Cisplatin is widely used as a conventional chemotherapy drug for lung adenocarcinoma (LUAD) patients. However, the chemical resistance greatly limits its therapeutic potential. The study aimed to uncover the specific role and new mechanisms of CPT1B in the cisplatin resistance of LUAD. Bioinformatics analysis was utilized to analyze the expression level and enriched pathway of CPT1B in LUAD. The expression of CPT1B in LUAD cells was determined by utilizing quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB). The cisplatin resistance in LUAD was measured with IC50 values obtained from the CCK-8 assay. We used the corresponding reagent kit and WB analysis to determine the levels of triglycerides, cholesterol, phospholipids, fatty acid β-oxidation (FAO) rate, and expression of lipid metabolism-related proteins. Finally, the regulation relationship between CPT1B and ZNF263 was confirmed through bioinformatics analysis, dual-luciferase, and chromatin immunoprecipitation assays. The present investigation revealed that CPT1B was upregulated in LUAD, participating in fatty acid metabolism pathways. In vitro studies have shown that upregulation of CPT1B promoted cisplatin resistance in LUAD cells. This promotion effect induced by the high expression of CPT1B on cisplatin resistance in LUAD was weakened after the addition of the FAO inhibitor Etomoxir. Mechanistically, ZNF263 was capable of binding to the promoter of CPT1B to activate its transcription, thereby enhancing FAO and promoting cisplatin resistance in LUAD cells. In summary, ZNF263 enhances cisplatin resistance in LUAD cells by upregulating CPT1B expression. This study enriches the molecular mechanisms of LUAD chemotherapy resistance and provides new directions for exploring therapeutic targets for LUAD.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Pharmacogenomics Journal
Pharmacogenomics Journal 医学-药学
CiteScore
7.20
自引率
0.00%
发文量
35
审稿时长
6-12 weeks
期刊介绍: The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.
期刊最新文献
Genetic association analysis and frequency of NUDT15*3 with thiopurine-induced myelosuppression in patients with inflammatory bowel disease in a large Dutch cohort. Plasma concentrations of venetoclax and Pharmacogenetics correlated with drug efficacy in treatment naive leukemia patients: a retrospective study. Polygenic score analyses on antidepressant response in late-life depression, results from the IRL-GRey study. Implementation of pharmacogenetic testing in pediatric oncology: barriers and facilitators assessment at eight Canadian academic health centres. Correction to: A pharmacogenomic study on the pharmacokinetics of tacrolimus in healthy subjects using the DMETTM Plus platform.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1