The folate cycle enzyme MTHFD2 induces cancer immune evasion through PD-L1 up-regulation

Shang, Ming; Yang, Huijie; Yang, Ran; Chen, Tao; Fu, Yuan; Li, Yeyi; Fang, Xianlong; Zhang, Kangjian; Jianju, Zhang; Li, Hui; Cao, Xueping; Gu, Jiande; Xiao, Jing; Zhang, Qi; Liu, Xinyuan; Yu, Qiujing; Wang, Ting

doi:10.1038/s41467-021-22173-5

Cited by 98 publications

(73 citation statements)

References 40 publications

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“…Proprotein convertase subtilisin/keying type 9 (PCSK9) has been documented to block intratumoural infiltration by T cells. 5 , 6 In the present study, we found that cholesterogenic cases expressed significantly higher levels of MTHFD2 and PCSK9 than other cases (Figure 2G ). Furthermore, as shown in Figure 2H , 10 pathways were significantly enriched in the cholesterogenic group (false discovery rate (FDR) < 0.05).…”

Section: Figuresupporting

confidence: 63%

Integrated mPD‐L1 and metabolic analysis identifies new prognostic subgroups in lung cancers with wild‐type EGFR

Wang

Chen

et al. 2021

Clinical & Translational Med

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Section: Figuresupporting

confidence: 63%

Integrated mPD‐L1 and metabolic analysis identifies new prognostic subgroups in lung cancers with wild‐type EGFR

Wang

Chen

et al. 2021

Clinical & Translational Med

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“…Among them, COX-2 is inductively expressed and is almost undetectable We also found that the NF-κB pathway can increase the expression of c-Myc to increase the expression of PD-L1. 22 Programmed death-ligand 1 (PD-L1, B7-H1) is a member of the B7 family of cell surface ligands. 23 It is a membrane ligand that is found significant upregulating on the surface of many cells in inflammatory and/or carcinogenic lesions.…”

Section: Discussionmentioning

confidence: 99%

circCORO1C promotes the proliferation and metastasis of hepatocellular carcinoma by enhancing the expression of PD‐L1 through NF‐κB pathway

Sun

Wen-ling

et al. 2021

Clinical Laboratory Analysis

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Background: Circular RNA (circRNA) affects the occurrence and development of human cancers, but the specific mechanism of hepatocellular carcinoma (HCC) has not yet been fully understood. Methods: CircRNAs were determined by human circRNA array analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell viability, migration, invasion, and other indicators were used for cell function analysis. Knockdown and overexpression techniques were used to explore the mechanism of circCORO1C in the occurrence and development of HCC by RNA sequencing, qRT-PCR, western blot, and other methods.Results: Among the thousands of circRNAs, 1238 circRNAs were significantly changed.As for the top 10 upregulated circRNAs, the expression of circRNAs, hsa_circ_0036412, hsa_circ_0036411, hsa_circ_0028071, hsa_circ_0036409, hsa_circ_0000437, hsa_ circ_0021427, hsa_circ_0097182, hsa_circ_0028067, hsa_circ_0006852, and hsa_ circ_0003620 were significantly increased. In regard to the top 10 downregulated circRNAs, the expression of hsa_circ_0123629, hsa_circ_0096121, hsa_circ_0038932, hsa-circRNA3310-44, hsa_circ_0045746, hsa_circ_0016836, hsa-circRNA10899-9, hsa_ circ_0050116, hsa_circ_0035543, and hsa_circ_0092118 decreased significantly. About these circRNAs, the downregulation of hsa_circ_0006852 (circCORO1C) can inhibit the tumorigenesis of HCC cells in vivo and in vitro, and the overexpression of circCORO1C can enhance the proliferation and metastasis ability of HCC cells. Mechanistically, circ-CORO1C activated the NF-κB signaling pathway, increased P65 phosphorylation and upregulation of c-Myc and COX-2, leading to increased PD-L1 expression. Conclusion:CircCORO1C upregulates c-Myc and COX-2 through NF-κB signaling pathway, leading to the upregulation of PD-L1, which jointly promotes the development of HCC, suggesting that circCORO1C is a promising biomarker and therapeutic target for HCC. How to cite this article: Wu F, Sun G, Zheng W, et al. circCORO1C promotes the proliferation and metastasis of hepatocellular carcinoma by enhancing the expression of

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“…Tumor-in ltrating immune cells in the TME can independently be adopt to predict sentinel lymph node status and patient survival, and the above ndings support a prognostic role of MTHFD2 in pan-cancer [4,24]. Therefore, we used TIMER to explore the association between immune in ltration levels and MTHFD2 expression level in various cancer types.…”

Section: Relationship Between Mthfd2 Expression and In Ltrating Immune Cells In Ovarian Cancermentioning

confidence: 96%

Up-Regulation of MTHFD2 is Associated With Clinicopathological Characteistics and Poor Survival in Ovarian Cancer, Possibly By Regulating MOB1A Signaling

Cui¹,

Su²,

Yang³

et al. 2021

Preprint

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Background: MTHFD2 is a folate-coupled metabolic enzyme, which has been proved to participant in the metabolic reprogramming and tumor cell-sustaining proliferative capacity. However, the function of MTHFD2 in the development of ovarian cancer and its potential molecular mechanisms is still unclear. Materials and methods: The expression, various mutations, prognosis, and related network signaling pathways of MTHFD2 were analyzed using bioinformatics-related websites, including Oncomine, GEPIA, UCSC, cBioPortal, KM Plotter, TISIDB and TIMER. The prognostic value of MTHFD2 expression was validated by our own ovarian cancer samples using RT-qPCR. The migration ad invasion of ovarian cancer cells were further analyzed by CCK-8 and transwell assay. The Western-blot assay was performed to explore the protein levels of MTHFD2 and MOB1A. Results: We obtained the following important results. (1) MTHFD2 expression was markedly up-regulated in ovarian cancer than normal samples. (2) Among patients with ovarian cancer, those with higher MTHFD2 expression was associated with lower survival rate. (3) The major mutation type of MTHFD2 in ovarian cancer samples was missense mutation. (4) MTHFD2 knockdown inhibited proliferation, migration, invasion, as well as the expression of MOB1A in vitro. Conclusion: MTHFD2, as a NAD+-dependent enzyme, accelerated tumor progression by up-regulating MBO1A, suggesting that this protein may be an independent prognostic factor and a potential therapeutic target for future ovarian cancer treatments.

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The folate cycle enzyme MTHFD2 induces cancer immune evasion through PD-L1 up-regulation

Cited by 98 publications

References 40 publications

Integrated mPD‐L1 and metabolic analysis identifies new prognostic subgroups in lung cancers with wild‐type EGFR

Integrated mPD‐L1 and metabolic analysis identifies new prognostic subgroups in lung cancers with wild‐type EGFR

circCORO1C promotes the proliferation and metastasis of hepatocellular carcinoma by enhancing the expression of PD‐L1 through NF‐κB pathway

Up-Regulation of MTHFD2 is Associated With Clinicopathological Characteistics and Poor Survival in Ovarian Cancer, Possibly By Regulating MOB1A Signaling

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