SIRT5 inhibits glycolysis and nasal type extranodal NK/T cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose-6-phosphate isomerase
Background: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a malignant tumor harboring a poor prognosis and unsatisfactory treatment outcomes. This study was performed to explore the pathogenesis and exact etiology of ENKTL. Methods Bioinformatic analysis was conducted to investiga...
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Elsevier
2025-01-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324003425 |
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| author | Tiansheng Wang Guolin Tan Ming Jiang Guohui Liu Wei Li Xiang Qing |
| author_facet | Tiansheng Wang Guolin Tan Ming Jiang Guohui Liu Wei Li Xiang Qing |
| author_sort | Tiansheng Wang |
| collection | DOAJ |
| description | Background: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a malignant tumor harboring a poor prognosis and unsatisfactory treatment outcomes. This study was performed to explore the pathogenesis and exact etiology of ENKTL. Methods Bioinformatic analysis was conducted to investigate the expression of SIRT5 and glucose-6-phosphate isomerase (GPI), as well their correlation with ENKTL overall survival. Cell proliferation ability and cell apoptosis were determined by CCK8, soft-agar colony formation and Tunel assays. Pyruvic acid and lactate production, GPI activity and F6P levels were detected to indicate glycolysis process. Succinylation modification in GPI protein was quantified by 4D label-free succinylation modification quantitative proteome. ENKTL mouse model was established by the injection of SNK6 cells. Results: SIRT5 suppressed the NKTL cell proliferation through the desuccinylation effect, while it was down-regulated in the ENKTL. SIRT5 catalyzed the desuccinylation of glycolytic enzyme GPI in ENKTL cells, which accelerated GPI protein degradation through the autophagy-lysosome system. SIRT5 inhibited glycolysis via mediating the desuccinylation of GPI, thereby suppressing ENKTL cell proliferation. The antitumor role of SIRT5 was also certified in ENKTL mouse model by targeting GPI. Conclusion: SIRT5 inhibits glycolysis via catalyzed the desuccinylation of glycolytic enzyme GPI, thereby repressing ENKTL cells proliferation and tumor growth. As SIRT5 serves as a tumor suppressor in ENKTL, it may be a promising molecular target in therapy strategy. |
| format | Article |
| id | doaj-art-a4ee3f2536044213a5f8cb3bc150088f |
| institution | OA Journals |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-a4ee3f2536044213a5f8cb3bc150088f2025-08-20T02:30:34ZengElsevierTranslational Oncology1936-52332025-01-015110221510.1016/j.tranon.2024.102215SIRT5 inhibits glycolysis and nasal type extranodal NK/T cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose-6-phosphate isomeraseTiansheng Wang0Guolin Tan1Ming Jiang2Guohui Liu3Wei Li4Xiang Qing5Department of Otolaryngology Head and Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Otolaryngology Head and Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Otolaryngology Head and Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Otolaryngology Head and Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, ChinaDepartment of Otolaryngology Head and Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Corresponding author.Background: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a malignant tumor harboring a poor prognosis and unsatisfactory treatment outcomes. This study was performed to explore the pathogenesis and exact etiology of ENKTL. Methods Bioinformatic analysis was conducted to investigate the expression of SIRT5 and glucose-6-phosphate isomerase (GPI), as well their correlation with ENKTL overall survival. Cell proliferation ability and cell apoptosis were determined by CCK8, soft-agar colony formation and Tunel assays. Pyruvic acid and lactate production, GPI activity and F6P levels were detected to indicate glycolysis process. Succinylation modification in GPI protein was quantified by 4D label-free succinylation modification quantitative proteome. ENKTL mouse model was established by the injection of SNK6 cells. Results: SIRT5 suppressed the NKTL cell proliferation through the desuccinylation effect, while it was down-regulated in the ENKTL. SIRT5 catalyzed the desuccinylation of glycolytic enzyme GPI in ENKTL cells, which accelerated GPI protein degradation through the autophagy-lysosome system. SIRT5 inhibited glycolysis via mediating the desuccinylation of GPI, thereby suppressing ENKTL cell proliferation. The antitumor role of SIRT5 was also certified in ENKTL mouse model by targeting GPI. Conclusion: SIRT5 inhibits glycolysis via catalyzed the desuccinylation of glycolytic enzyme GPI, thereby repressing ENKTL cells proliferation and tumor growth. As SIRT5 serves as a tumor suppressor in ENKTL, it may be a promising molecular target in therapy strategy.http://www.sciencedirect.com/science/article/pii/S1936523324003425ENKTLSIRT5GPIGlycolysisDesuccinylationCell proliferation |
| spellingShingle | Tiansheng Wang Guolin Tan Ming Jiang Guohui Liu Wei Li Xiang Qing SIRT5 inhibits glycolysis and nasal type extranodal NK/T cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose-6-phosphate isomerase Translational Oncology ENKTL SIRT5 GPI Glycolysis Desuccinylation Cell proliferation |
| title | SIRT5 inhibits glycolysis and nasal type extranodal NK/T cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose-6-phosphate isomerase |
| title_full | SIRT5 inhibits glycolysis and nasal type extranodal NK/T cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose-6-phosphate isomerase |
| title_fullStr | SIRT5 inhibits glycolysis and nasal type extranodal NK/T cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose-6-phosphate isomerase |
| title_full_unstemmed | SIRT5 inhibits glycolysis and nasal type extranodal NK/T cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose-6-phosphate isomerase |
| title_short | SIRT5 inhibits glycolysis and nasal type extranodal NK/T cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose-6-phosphate isomerase |
| title_sort | sirt5 inhibits glycolysis and nasal type extranodal nk t cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose 6 phosphate isomerase |
| topic | ENKTL SIRT5 GPI Glycolysis Desuccinylation Cell proliferation |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324003425 |
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