دورية أكاديمية
Up-regulation of NMRK2 mediated by TFE3 fusions is the key for energy metabolism adaption of Xp11.2 translocation renal cell carcinoma.
العنوان: | Up-regulation of NMRK2 mediated by TFE3 fusions is the key for energy metabolism adaption of Xp11.2 translocation renal cell carcinoma. |
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المؤلفون: | Chen Y; Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China., Yang L; Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China., Lu Y; Department of Urology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, Jiangsu, 210008, China., Liu N; Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210001, China., Ma W; Department of Urology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, Jiangsu, 210008, China., Fan H; Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China., Hu Q; Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China., Han X; Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China., Gan W; Department of Urology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, Jiangsu, 210008, China. Electronic address: gwd@nju.edu.cn., Li D; Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address: lidm@nju.edu.cn. |
المصدر: | Cancer letters [Cancer Lett] 2022 Jul 10; Vol. 538, pp. 215689. Date of Electronic Publication: 2022 Apr 18. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Limerick : Elsevier Science Ireland Original Publication: Amsterdam, Elsevier/North-Holland. |
مواضيع طبية MeSH: | Basic Helix-Loop-Helix Leucine Zipper Transcription Factors*/genetics , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors*/metabolism , Carcinoma, Renal Cell*/pathology , Intracellular Signaling Peptides and Proteins*/metabolism , Kidney Neoplasms*/pathology , Phosphotransferases (Alcohol Group Acceptor)*/genetics , Phosphotransferases (Alcohol Group Acceptor)*/metabolism, Glycolysis ; Humans ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; Translocation, Genetic ; Up-Regulation |
مستخلص: | Due to the inadequate awareness of Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC), its metabolic features have not been described. Here, by using nontargeted LC-MS-based metabolomics, we found that the chimeric TFE3 protein, the major oncogenic driver in Xp11.2 tRCC, regulated the metabolic pathways in Xp11.2 tRCC, including glycerophospholipid metabolism, purine metabolism, amino acid metabolism, fatty acid metabolism and energy metabolism. Combined with our present metabolomic data and previous studies, it was found that Xp11.2 tRCC preferred mitochondrial respiration, which was obviously different from renal clear cell carcinoma (ccRCC). Furthermore, by using bioinformatics and data mining, NMRK2, an important target for energy metabolism adaptation of Xp11.2 tRCC, was identified. Additionally, we confirmed that chimeric TFE3 could transcriptionally activate the expression of NMRK2, but the NONO-TFE3 fusion, which lacks the activation domain encoded by exons 4-5 of the TFE3 gene, functioned as a transcription factor by recruiting TFEB. When NMRK2 was knocked down, the mitochondrial respiration of Xp11.2 tRCC, rather than glycolysis, was significantly weakened. Therefore, the present study revealed the mechanism of the energy metabolism adaptation by which the TFE3 fusion promotes mitochondrial respiration by upregulating NMRK2 in Xp11.2 tRCC. (Copyright © 2022 Elsevier B.V. All rights reserved.) |
فهرسة مساهمة: | Keywords: Chimeric TFE3 protein; Metabolic characteristic; Mitochondrial respiration; NMRK2; Transcriptional activation; Xp11.2 tRCC |
المشرفين على المادة: | 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors) 0 (Intracellular Signaling Peptides and Proteins) 0 (Oncogene Proteins, Fusion) 0 (TFE3 protein, human) EC 2.7.1.- (NMRK2 protein, human) EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)) |
تواريخ الأحداث: | Date Created: 20220421 Date Completed: 20220517 Latest Revision: 20220721 |
رمز التحديث: | 20221213 |
DOI: | 10.1016/j.canlet.2022.215689 |
PMID: | 35447281 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1872-7980 |
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DOI: | 10.1016/j.canlet.2022.215689 |