NMRK2 是 Xp11.2 易位肾细胞癌的有效诊断指标。

IF 5.6 2区 医学 Q1 ONCOLOGY
Huayi Feng, Shouqing Cao, Shihui Fu, Junxiao Liu, Yu Gao, Zhouhuan Dong, Tianwei Cai, Lequan Wen, Zhuang Xiong, Shangwei Li, Xu Zhang, Xin Ma, Xiubin Li
{"title":"NMRK2 是 Xp11.2 易位肾细胞癌的有效诊断指标。","authors":"Huayi Feng,&nbsp;Shouqing Cao,&nbsp;Shihui Fu,&nbsp;Junxiao Liu,&nbsp;Yu Gao,&nbsp;Zhouhuan Dong,&nbsp;Tianwei Cai,&nbsp;Lequan Wen,&nbsp;Zhuang Xiong,&nbsp;Shangwei Li,&nbsp;Xu Zhang,&nbsp;Xin Ma,&nbsp;Xiubin Li","doi":"10.1002/path.6340","DOIUrl":null,"url":null,"abstract":"<p>Xp11.2 translocation renal cell carcinomas (tRCC) are a rare and highly malignant type of renal cancer, lacking efficient diagnostic indicators and therapeutic targets. Through the analysis of public databases and our cohort, we identified NMRK2 as a potential diagnostic marker for distinguishing Xp11.2 tRCC from kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) due to its specific upregulation in Xp11.2 tRCC tissues. Mechanistically, we discovered that TFE3 fusion protein binds to the promoter of the NMRK2 gene, leading to its upregulation. Importantly, we established RNA- and protein-based diagnostic methods for identifying Xp11.2 tRCC based on NMRK2 expression levels, and the diagnostic performance of our methods was comparable to a dual-color break-apart fluorescence <i>in situ</i> hybridization assay. Moreover, we successfully identified fresh Xp11.2 tRCC tissues after surgical excision using our diagnostic methods and established an immortalized Xp11.2 tRCC cell line for further research purposes. Functional studies revealed that NMRK2 promotes the progression of Xp11.2 tRCC by upregulating the NAD<sup>+</sup>/NADH ratio, and supplementation with β-nicotinamide mononucleotide (NMN) or nicotinamide riboside chloride (NR), effectively rescued the phenotypes induced by the knockdown of NMRK2 in Xp11.2 tRCC. Taken together, these data introduce a new diagnostic indicator capable of accurately distinguishing Xp11.2 tRCC and highlight the possibility of developing novel targeted therapeutics. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"264 2","pages":"228-240"},"PeriodicalIF":5.6000,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"NMRK2 is an efficient diagnostic indicator for Xp11.2 translocation renal cell carcinoma\",\"authors\":\"Huayi Feng,&nbsp;Shouqing Cao,&nbsp;Shihui Fu,&nbsp;Junxiao Liu,&nbsp;Yu Gao,&nbsp;Zhouhuan Dong,&nbsp;Tianwei Cai,&nbsp;Lequan Wen,&nbsp;Zhuang Xiong,&nbsp;Shangwei Li,&nbsp;Xu Zhang,&nbsp;Xin Ma,&nbsp;Xiubin Li\",\"doi\":\"10.1002/path.6340\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Xp11.2 translocation renal cell carcinomas (tRCC) are a rare and highly malignant type of renal cancer, lacking efficient diagnostic indicators and therapeutic targets. Through the analysis of public databases and our cohort, we identified NMRK2 as a potential diagnostic marker for distinguishing Xp11.2 tRCC from kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) due to its specific upregulation in Xp11.2 tRCC tissues. Mechanistically, we discovered that TFE3 fusion protein binds to the promoter of the NMRK2 gene, leading to its upregulation. Importantly, we established RNA- and protein-based diagnostic methods for identifying Xp11.2 tRCC based on NMRK2 expression levels, and the diagnostic performance of our methods was comparable to a dual-color break-apart fluorescence <i>in situ</i> hybridization assay. Moreover, we successfully identified fresh Xp11.2 tRCC tissues after surgical excision using our diagnostic methods and established an immortalized Xp11.2 tRCC cell line for further research purposes. Functional studies revealed that NMRK2 promotes the progression of Xp11.2 tRCC by upregulating the NAD<sup>+</sup>/NADH ratio, and supplementation with β-nicotinamide mononucleotide (NMN) or nicotinamide riboside chloride (NR), effectively rescued the phenotypes induced by the knockdown of NMRK2 in Xp11.2 tRCC. Taken together, these data introduce a new diagnostic indicator capable of accurately distinguishing Xp11.2 tRCC and highlight the possibility of developing novel targeted therapeutics. © 2024 The Pathological Society of Great Britain and Ireland.</p>\",\"PeriodicalId\":232,\"journal\":{\"name\":\"The Journal of Pathology\",\"volume\":\"264 2\",\"pages\":\"228-240\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2024-08-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/path.6340\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Pathology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/path.6340","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

Xp11.2易位肾细胞癌(tRCC)是一种罕见的高度恶性肾癌,缺乏有效的诊断指标和治疗靶点。通过分析公共数据库和我们的队列,我们发现NMRK2是区分Xp11.2 tRCC与肾透明细胞癌(KIRC)和肾乳头状细胞癌(KIRP)的潜在诊断标志物,因为它在Xp11.2 tRCC组织中特异性上调。从机理上讲,我们发现 TFE3 融合蛋白与 NMRK2 基因启动子结合,导致其上调。重要的是,我们根据NMRK2的表达水平建立了基于RNA和蛋白质的诊断方法来鉴别Xp11.2 tRCC,其诊断效果与双色断裂荧光原位杂交检测法相当。此外,我们还利用诊断方法成功鉴定了手术切除后的新鲜Xp11.2 tRCC组织,并建立了永生化的Xp11.2 tRCC细胞系用于进一步研究。功能研究发现,NMRK2通过上调NAD+/NADH比值促进Xp11.2 tRCC的进展,而补充β-烟酰胺单核苷酸(NMN)或氯化烟酰胺核糖苷(NR)可有效挽救NMRK2敲除在Xp11.2 tRCC中诱导的表型。总之,这些数据提出了一种新的诊断指标,能够准确区分Xp11.2 tRCC,并强调了开发新型靶向疗法的可能性。© 2024 大不列颠及爱尔兰病理学会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
NMRK2 is an efficient diagnostic indicator for Xp11.2 translocation renal cell carcinoma

Xp11.2 translocation renal cell carcinomas (tRCC) are a rare and highly malignant type of renal cancer, lacking efficient diagnostic indicators and therapeutic targets. Through the analysis of public databases and our cohort, we identified NMRK2 as a potential diagnostic marker for distinguishing Xp11.2 tRCC from kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) due to its specific upregulation in Xp11.2 tRCC tissues. Mechanistically, we discovered that TFE3 fusion protein binds to the promoter of the NMRK2 gene, leading to its upregulation. Importantly, we established RNA- and protein-based diagnostic methods for identifying Xp11.2 tRCC based on NMRK2 expression levels, and the diagnostic performance of our methods was comparable to a dual-color break-apart fluorescence in situ hybridization assay. Moreover, we successfully identified fresh Xp11.2 tRCC tissues after surgical excision using our diagnostic methods and established an immortalized Xp11.2 tRCC cell line for further research purposes. Functional studies revealed that NMRK2 promotes the progression of Xp11.2 tRCC by upregulating the NAD+/NADH ratio, and supplementation with β-nicotinamide mononucleotide (NMN) or nicotinamide riboside chloride (NR), effectively rescued the phenotypes induced by the knockdown of NMRK2 in Xp11.2 tRCC. Taken together, these data introduce a new diagnostic indicator capable of accurately distinguishing Xp11.2 tRCC and highlight the possibility of developing novel targeted therapeutics. © 2024 The Pathological Society of Great Britain and Ireland.

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
The Journal of Pathology
The Journal of Pathology 医学-病理学
CiteScore
14.10
自引率
1.40%
发文量
144
审稿时长
3-8 weeks
期刊介绍: The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease. The Journal of Pathology welcomes investigative studies on human tissues, in vitro and in vivo experimental studies, and investigations based on animal models with a clear relevance to human disease, including transgenic systems. As well as original research papers, the Journal seeks to provide rapid publication in a variety of other formats, including editorials, review articles, commentaries and perspectives and other features, both contributed and solicited.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信