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| Natura: | Artículo Open Access |
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Wiley
2024
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| Accesso online: | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6340 |
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| _version_ | 1867014097908793344 |
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| author | 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 |
| author_facet | 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 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 |
| collection | Wiley Open Access |
| contents | NMRK2 is an efficient diagnostic indicator for Xp11.2 translocation renal cell carcinoma 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 The Journal of Pathology AbstractXp11.2 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. 10.1002/path.6340 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/path.6340 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_path_6340 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | NMRK2 is an efficient diagnostic indicator for Xp11.2 translocation renal cell carcinoma 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 The Journal of Pathology NMRK2 is an efficient diagnostic indicator for Xp11.2 translocation renal cell carcinoma 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 The Journal of Pathology AbstractXp11.2 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. 10.1002/path.6340 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | NMRK2 is an efficient diagnostic indicator for Xp11.2 translocation renal cell carcinoma |
| topic | The Journal of Pathology |
| url | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6340 |