A Nicotinamide Phosphoribosyltransferase Inhibitor, FK866, Suppresses the Growth of Anaplastic Meningiomas and Inhibits Immune Checkpoint Expression by Regulating STAT1
Anaplastic meningioma is classified as a World Health Organization (WHO) grade III tumor and shows a strong tendency to recur. Although the incidence of anaplastic meningioma is low, the high rate of recurrence and death still makes treatment a challenge. A proteomics analysis was performed to inves...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.836257/full |
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| author | Yuxuan Deng Boyi Hu Yazhou Miao Jing Wang Shaodong Zhang Hong Wan Zhen Wu Yifan Lv Jie Feng Nan Ji Deric Park Shuyu Hao |
| author_facet | Yuxuan Deng Boyi Hu Yazhou Miao Jing Wang Shaodong Zhang Hong Wan Zhen Wu Yifan Lv Jie Feng Nan Ji Deric Park Shuyu Hao |
| author_sort | Yuxuan Deng |
| collection | DOAJ |
| description | Anaplastic meningioma is classified as a World Health Organization (WHO) grade III tumor and shows a strong tendency to recur. Although the incidence of anaplastic meningioma is low, the high rate of recurrence and death still makes treatment a challenge. A proteomics analysis was performed to investigate the differentially expressed proteins between anaplastic meningiomas and fibrous meningiomas by micro-LC-MS/MS. The key metabolic enzyme nicotinamide phosphoribosyltransferase (NAMPT) showed upregulated expression in anaplastic meningiomas. However, targeting NAMPT to treat anaplastic meningiomas has not been reported. In vitro, NAMPT inhibitor -FK866 reduced the viability of anaplastic meningiomas by inducing cell cycle arrest at the G2/M phase. Intriguingly, the NAMPT inhibitor -FK866 decreased the protein expression of immune checkpoints PD-L1 and B7-H3 by down-regulating the STAT1 and p-STAT1 expression in vitro. Furthermore, FK866 suppressed the growth of anaplastic meningiomas in an in vivo xenograft model. The expression of Ki-67 and immune checkpoint proteins (PD-L1 and B7-H3) showed significant differences between the group treated with FK866 and the control group treated with DMSO. In conclusion, the expression of NAMPT, which plays a crucial role in energy metabolism, was upregulated in anaplastic meningiomas. The NAMPT inhibitor -FK866 significantly suppressed the growth of anaplastic meningiomas in vitro and in vivo. More strikingly, FK866 potently inhibited immune checkpoint protein (PD-L1 and B7-H3) expression by regulating STAT1 in vitro and in vivo. Our results demonstrated that NAMPT inhibitors could potentially be an effective treatment method for patients suffering from anaplastic meningiomas. |
| first_indexed | 2024-04-14T07:38:03Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-14T07:38:03Z |
| publishDate | 2022-04-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-e3605a1b5cab4e88b44cc83098c329022022-12-22T02:05:37ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-04-011210.3389/fonc.2022.836257836257A Nicotinamide Phosphoribosyltransferase Inhibitor, FK866, Suppresses the Growth of Anaplastic Meningiomas and Inhibits Immune Checkpoint Expression by Regulating STAT1Yuxuan Deng0Boyi Hu1Yazhou Miao2Jing Wang3Shaodong Zhang4Hong Wan5Zhen Wu6Yifan Lv7Jie Feng8Nan Ji9Deric Park10Shuyu Hao11Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, University of Chicago Medical Center, Chicago, IL, United StatesDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaAnaplastic meningioma is classified as a World Health Organization (WHO) grade III tumor and shows a strong tendency to recur. Although the incidence of anaplastic meningioma is low, the high rate of recurrence and death still makes treatment a challenge. A proteomics analysis was performed to investigate the differentially expressed proteins between anaplastic meningiomas and fibrous meningiomas by micro-LC-MS/MS. The key metabolic enzyme nicotinamide phosphoribosyltransferase (NAMPT) showed upregulated expression in anaplastic meningiomas. However, targeting NAMPT to treat anaplastic meningiomas has not been reported. In vitro, NAMPT inhibitor -FK866 reduced the viability of anaplastic meningiomas by inducing cell cycle arrest at the G2/M phase. Intriguingly, the NAMPT inhibitor -FK866 decreased the protein expression of immune checkpoints PD-L1 and B7-H3 by down-regulating the STAT1 and p-STAT1 expression in vitro. Furthermore, FK866 suppressed the growth of anaplastic meningiomas in an in vivo xenograft model. The expression of Ki-67 and immune checkpoint proteins (PD-L1 and B7-H3) showed significant differences between the group treated with FK866 and the control group treated with DMSO. In conclusion, the expression of NAMPT, which plays a crucial role in energy metabolism, was upregulated in anaplastic meningiomas. The NAMPT inhibitor -FK866 significantly suppressed the growth of anaplastic meningiomas in vitro and in vivo. More strikingly, FK866 potently inhibited immune checkpoint protein (PD-L1 and B7-H3) expression by regulating STAT1 in vitro and in vivo. Our results demonstrated that NAMPT inhibitors could potentially be an effective treatment method for patients suffering from anaplastic meningiomas.https://www.frontiersin.org/articles/10.3389/fonc.2022.836257/fullanaplastic meningiomaNAMPTNAMPT inhibitorimmune checkpointcell cycleproteomics |
| spellingShingle | Yuxuan Deng Boyi Hu Yazhou Miao Jing Wang Shaodong Zhang Hong Wan Zhen Wu Yifan Lv Jie Feng Nan Ji Deric Park Shuyu Hao A Nicotinamide Phosphoribosyltransferase Inhibitor, FK866, Suppresses the Growth of Anaplastic Meningiomas and Inhibits Immune Checkpoint Expression by Regulating STAT1 Frontiers in Oncology anaplastic meningioma NAMPT NAMPT inhibitor immune checkpoint cell cycle proteomics |
| title | A Nicotinamide Phosphoribosyltransferase Inhibitor, FK866, Suppresses the Growth of Anaplastic Meningiomas and Inhibits Immune Checkpoint Expression by Regulating STAT1 |
| title_full | A Nicotinamide Phosphoribosyltransferase Inhibitor, FK866, Suppresses the Growth of Anaplastic Meningiomas and Inhibits Immune Checkpoint Expression by Regulating STAT1 |
| title_fullStr | A Nicotinamide Phosphoribosyltransferase Inhibitor, FK866, Suppresses the Growth of Anaplastic Meningiomas and Inhibits Immune Checkpoint Expression by Regulating STAT1 |
| title_full_unstemmed | A Nicotinamide Phosphoribosyltransferase Inhibitor, FK866, Suppresses the Growth of Anaplastic Meningiomas and Inhibits Immune Checkpoint Expression by Regulating STAT1 |
| title_short | A Nicotinamide Phosphoribosyltransferase Inhibitor, FK866, Suppresses the Growth of Anaplastic Meningiomas and Inhibits Immune Checkpoint Expression by Regulating STAT1 |
| title_sort | nicotinamide phosphoribosyltransferase inhibitor fk866 suppresses the growth of anaplastic meningiomas and inhibits immune checkpoint expression by regulating stat1 |
| topic | anaplastic meningioma NAMPT NAMPT inhibitor immune checkpoint cell cycle proteomics |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.836257/full |
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