核 TOP1MT 在 HNSCC 中通过伪基因产生顺铂抗性

Journal of dental research Pub Date : 2024-11-01 Epub Date: 2024-10-09 DOI:10.1177/00220345241272017
T Tong, P S Zhai, X Qin, Z Zhang, C W Li, H Y Guo, H L Ma
{"title":"核 TOP1MT 在 HNSCC 中通过伪基因产生顺铂抗性","authors":"T Tong, P S Zhai, X Qin, Z Zhang, C W Li, H Y Guo, H L Ma","doi":"10.1177/00220345241272017","DOIUrl":null,"url":null,"abstract":"<p><p>Cisplatin resistance is one of the major causes of treatment failure in head and neck squamous cell carcinoma (HNSCC). There is an urgent need to uncover the underlying mechanism for developing effective treatment strategies. A quantitative proteomics assay was used to identify differential proteins in cisplatin-resistant cells. Mitochondrial topoisomerase I (TOP1MT) localization was determined using laser confocal microscopy and nucleocytoplasmic separation assay. Chromatin immunoprecipitation sequencing, dual-luciferase reporter assay, and RNA immunoprecipitation were used to identify the interaction between pseudogenes, miRNAs, and real genes. In vivo experiments verified the interaction between TOP1MT and pseudogenes on cisplatin resistance. TOP1MT was identified as a driving factor of cisplatin resistance in vitro, in vivo, and in HNSCC patients. Moreover, TOP1MT exceptionally translocated to the nucleus in cisplatin-resistant HNSCC cells in a signal peptide-dependent manner. Nuclear TOP1MT (nTOP1MT) transcriptionally regulated the mitochondrial functional pseudogene MTATP6P1, which bound to miR-137 and miR-491-5p as a competing endogenous RNA (ceRNA) and promoted the expression of MTATP6. An increase in MTATP6 enhanced mitochondrial oxidative phosphorylation (OXPHOS), which conferred cisplatin resistance in HNSCC. Our findings revealed that nTOP1MT transcriptionally activated MTAPT6P1 and increased MTATP6 expression via ceRNA, which facilitated OXPHOS and cisplatin resistance. These results provide novel insight for overcoming cisplatin resistance in HNSCC.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1238-1248"},"PeriodicalIF":0.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Nuclear TOP1MT Confers Cisplatin Resistance via Pseudogene in HNSCC.\",\"authors\":\"T Tong, P S Zhai, X Qin, Z Zhang, C W Li, H Y Guo, H L Ma\",\"doi\":\"10.1177/00220345241272017\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cisplatin resistance is one of the major causes of treatment failure in head and neck squamous cell carcinoma (HNSCC). There is an urgent need to uncover the underlying mechanism for developing effective treatment strategies. A quantitative proteomics assay was used to identify differential proteins in cisplatin-resistant cells. Mitochondrial topoisomerase I (TOP1MT) localization was determined using laser confocal microscopy and nucleocytoplasmic separation assay. Chromatin immunoprecipitation sequencing, dual-luciferase reporter assay, and RNA immunoprecipitation were used to identify the interaction between pseudogenes, miRNAs, and real genes. In vivo experiments verified the interaction between TOP1MT and pseudogenes on cisplatin resistance. TOP1MT was identified as a driving factor of cisplatin resistance in vitro, in vivo, and in HNSCC patients. Moreover, TOP1MT exceptionally translocated to the nucleus in cisplatin-resistant HNSCC cells in a signal peptide-dependent manner. Nuclear TOP1MT (nTOP1MT) transcriptionally regulated the mitochondrial functional pseudogene MTATP6P1, which bound to miR-137 and miR-491-5p as a competing endogenous RNA (ceRNA) and promoted the expression of MTATP6. An increase in MTATP6 enhanced mitochondrial oxidative phosphorylation (OXPHOS), which conferred cisplatin resistance in HNSCC. Our findings revealed that nTOP1MT transcriptionally activated MTAPT6P1 and increased MTATP6 expression via ceRNA, which facilitated OXPHOS and cisplatin resistance. These results provide novel insight for overcoming cisplatin resistance in HNSCC.</p>\",\"PeriodicalId\":94075,\"journal\":{\"name\":\"Journal of dental research\",\"volume\":\" \",\"pages\":\"1238-1248\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of dental research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/00220345241272017\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/9 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of dental research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/00220345241272017","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/9 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

顺铂耐药性是头颈部鳞状细胞癌(HNSCC)治疗失败的主要原因之一。目前迫切需要揭示其潜在机制,以制定有效的治疗策略。本研究采用定量蛋白质组学分析方法来鉴定顺铂耐药细胞中的差异蛋白质。线粒体拓扑异构酶I(TOP1MT)的定位是通过激光共聚焦显微镜和核胞质分离试验确定的。染色质免疫共沉淀测序、双荧光素酶报告分析和 RNA 免疫共沉淀被用来鉴定伪基因、miRNA 和真基因之间的相互作用。体内实验验证了 TOP1MT 与伪基因之间在顺铂抗性上的相互作用。在体外、体内和 HNSCC 患者中,TOP1MT 被确定为顺铂耐药性的驱动因素。此外,在顺铂耐药的 HNSCC 细胞中,TOP1MT 例外地以信号肽依赖的方式转位到细胞核中。核TOP1MT(nTOP1MT)转录调控线粒体功能假基因MTATP6P1,MTATP6P1作为竞争性内源性RNA(ceRNA)与miR-137和miR-491-5p结合,促进MTATP6的表达。MTATP6的增加增强了线粒体氧化磷酸化(OXPHOS),从而赋予了HNSCC顺铂抗性。我们的研究结果表明,nTOP1MT可通过ceRNA转录激活MTAPT6P1并增加MTATP6的表达,从而促进OXPHOS和顺铂抗性。这些结果为克服 HNSCC 的顺铂耐药性提供了新的见解。
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
Nuclear TOP1MT Confers Cisplatin Resistance via Pseudogene in HNSCC.

Cisplatin resistance is one of the major causes of treatment failure in head and neck squamous cell carcinoma (HNSCC). There is an urgent need to uncover the underlying mechanism for developing effective treatment strategies. A quantitative proteomics assay was used to identify differential proteins in cisplatin-resistant cells. Mitochondrial topoisomerase I (TOP1MT) localization was determined using laser confocal microscopy and nucleocytoplasmic separation assay. Chromatin immunoprecipitation sequencing, dual-luciferase reporter assay, and RNA immunoprecipitation were used to identify the interaction between pseudogenes, miRNAs, and real genes. In vivo experiments verified the interaction between TOP1MT and pseudogenes on cisplatin resistance. TOP1MT was identified as a driving factor of cisplatin resistance in vitro, in vivo, and in HNSCC patients. Moreover, TOP1MT exceptionally translocated to the nucleus in cisplatin-resistant HNSCC cells in a signal peptide-dependent manner. Nuclear TOP1MT (nTOP1MT) transcriptionally regulated the mitochondrial functional pseudogene MTATP6P1, which bound to miR-137 and miR-491-5p as a competing endogenous RNA (ceRNA) and promoted the expression of MTATP6. An increase in MTATP6 enhanced mitochondrial oxidative phosphorylation (OXPHOS), which conferred cisplatin resistance in HNSCC. Our findings revealed that nTOP1MT transcriptionally activated MTAPT6P1 and increased MTATP6 expression via ceRNA, which facilitated OXPHOS and cisplatin resistance. These results provide novel insight for overcoming cisplatin resistance in HNSCC.

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
自引率
0.00%
发文量
0
期刊最新文献
KDM6B-Mediated HADHA Demethylation/Lactylation Regulates Cementogenesis. System Dynamics Modeling of Caries Severity States in Long-Term Care. Terahertz Imaging Detects Oral Cariogenic Microbial Domains Characteristics. Explainable Deep Learning Approaches for Risk Screening of Periodontitis. Geo-Net: Geometry-Guided Pretraining for Tooth Point Cloud Segmentation.
×
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