［1］CHRISTENSEN KE,MACKENZIE RE.Mitochondrial methylenetetrahydrofolate dehydrogenase,methenyltetrahydrofolate cyclohydrolase,and formyltetrahydrofolate synthetases［J］.Vitamins and hormones,2008,79:393.
［2］NILSSON R,JAIN M,MADHUSUDHAN N,et al.Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer［J］.Nature Communications,2014,5(1):3128.
［3］LI G,WU J,LI L,et al.p53 deficiency induces MTHFD2 transcription to promote cell proliferation and restrain DNA damage［J］.Proceedings of the National Academy of Sciences,2021,118(28):e2019822118.
［4］LIU X,HUANG Y,LIAO H,et al.The preliminary study on the function of methylenetetrahydrofolate dehydrogenase 2 in hepatocellular carcinoma［J］.Natl Med J China,2015,95(48):3908-3911.
［5］KOSEKI J,KONNO M,ASAI A,et al.Enzymes of the one-carbon folate metabolism as anticancer targets predicted by survival rate analysis［J］.Scientific Reports,2018,8(1):303.
［6］HE H,LI P,JIA W,et al.High expression of methylenetetrahydrofolate dehydrogenase 2(MTHFD2) in esophageal squamous cell carcinoma and its clinical prognostic significance［J］.Medical Science Monitor,2020,26:e920259.
［7］NISHIMURA T,NAKATA A,CHEN X,et al.Cancer stem-like properties and gefitinib resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD2［J］.Oncogene,2019,38(14):2464-2481.
［8］CHENG W,CHANG C,LO C,et al.Identification of theranostic factors for patients developing metastasis after surgery for early-stage lung adenocarcinoma［J］.Theranostics,2021,11(8):3661-3675.
［9］CUI X,SU H,YANG J,et al.Up-regulation of MTHFD2 is associated with clinicopathological characteristics and poor survival in ovarian cancer,possibly by regulating MOB1A signaling［J］.Journal of Ovarian Research,2022,15(1):23.
［10］NOGUCHI K,KONNO M,KOSEKI J,et al.The mitochondrial one-carbon metabolic pathway is associated with patient survival in pancreatic cancer［J］.Oncology Letters,2018,16(2):1827-1834.
［11］SELCUKLU SD,DONOGHUE MTA,REHMET K,et al.MicroRNA-9 inhibition of cell proliferation and identification of novel miR-9 targets by transcriptome profiling in breast cancer cells［J］.Journal of Biological Chemistry,2012,287(35):29516-29528.
［12］LIN H,HUANG B,WANG H,et al.MTHFD2 overexpression predicts poor prognosis in renal cell carcinoma and is associated with cell proliferation and vimentin-modulated migration and invasion［J］.Cellular Physiology and Biochemistry,2018,51(2):991-1000.
［13］GREEN NH,GALVAN DL,BADAL SS,et al.MTHFD2 links RNA methylation to metabolic reprogramming in renal cell carcinoma［J］.Oncogene,2019,38(34):6211-6225.
［14］PIKMAN Y,PUISSANT A,ALEXE G,et al.Targeting MTHFD2 in acute myeloid leukemia［J］.Journal of Experimental Medicine,2016,213(7):1285-1306.
［15］CHAN C,WU C,DUBEY NK,et al.Modulating redox homeostasis and cellular reprogramming through inhibited methylenetetrahydrofolate dehydrogenase 2 enzymatic activities in lung cancer［J］.Aging,2020,12(18):17930-17947.
［16］SHI Y,XU Y,YAO J,et al.MTHFD2 promotes tumorigenesis and metastasis in lung adenocarcinoma by regulating AKT/GSK-3β/β-catenin signalling［J］.Journal of Cellular and Molecular Medicine,2021,25(14):7013-7027.
［17］PALLMANN N,DENG K,LIVGARD M,et al.Stress-mediated reprogramming of prostate cancer one-carbon cycle drives disease progression［J］.Cancer Research,2021,81(15):4066-4078.
［18］TANAKA K,SASAYAMA T,NAGASHIMA H,et al.Glioma cells require one-carbon metabolism to survive glutamine starvation［J］.Acta Neuropathologica Communications,2021,9(1):16.
［19］KOUFARIS C,GALLAGE S,YANG T,et al.Suppression of MTHFD2 in MCF-7 breast cancer cells increases glycolysis,dependency on exogenous glycine,and sensitivity to folate depletion［J］.Journal of Proteome Research,2016,15(8):2618-2625.
［20］SHIN M,MOMB J,APPLING DR.Human mitochondrial MTHFD2 is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase［J］.Cancer & Metabolism,2017,5(1):11.
［21］WANG LW,SHEN H,NOBRE L,et al.Epstein-barr-virus-induced one-carbon metabolism drives B cell transformation［J］.Cell Metabolism,2019,30(3):539-555.
［22］JU H,LU Y,CHEN D,et al.Modulation of redox homeostasis by inhibition of MTHFD2 in colorectal cancer:Mechanisms and therapeutic implications［J］.Journal of the National Cancer Institute,2019,111(6):584-596.
［23］GUSTAFSSON SHEPPARD N,JARL L,MAHADESSIAN D,et al.The folate-coupled enzyme MTHFD2 is a nuclear protein and promotes cell proliferation［J］.Scientific Reports,2015,5(1):15029.
［24］KOUFARIS C,NILSSON R.Protein interaction and functional data indicate MTHFD2 involvement in RNA processing and translation［J］.Cancer & Metabolism,2018,6(1):12.
［25］LEHTINEN L,KETOLA K,MAKELA R,et al.High-throughput RNAi screening for novel modulators of vimentin expression identifies MTHFD2 as a regulator of breast cancer cell migration and invasion［J］.Oncotarget,2013,4(1):48-63.
［26］LI Q,YANG F,SHI X,et al.MTHFD2 promotes ovarian cancer growth and metastasis via activation of the STAT3 signaling pathway［J］.FEBS Open Bio,2021,11(10):2845-2857.
［27］YU C,YANG L,CAI M,et al.Down-regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle-related genes［J］.Journal of Cellular and Molecular Medicine,2020,24(2):1568-1577.
［28］LIU X,LIU S,PIAO C,et al.Non-metabolic function of MTHFD2 activates CDK2 in bladder cancer［J］.Cancer Science,2021,112(12):4909-4919.
［29］HUANG J,QIN Y,LIN C,et al.MTHFD2 facilitates breast cancer cell proliferation via the AKT signaling pathway［J］.Experimental and Therapeutic Medicine,2021,22(1):703.
［30］SHANG M,YANG H,YANG R,et al.The folate cycle enzyme MTHFD2 induces cancer immune evasion through PD-L1 up-regulation［J］.Nature Communications,2021,12(1):1940.
［31］BEN-SAHRA I,HOXHAJ G,RICOULT SJH,et al.mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle［J］.Science,2016,351(6274):728-733.
［32］MORAN DM,TRUSK PB,PRY K,et al.KRAS mutation status is associated with enhanced dependency on folate metabolism pathways in non-small cell lung cancer cells［J］.Molecular Cancer Therapeutics,2014,13(6):1611-1624.
［33］CHEUNG CHY,HSU C,TSUEI C,et al.Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy［J］.Cell Death & Disease,2019,10(11):786.
［34］SEN N,CROSS AM,LORENZI PL,et al.EWS-FLI1 reprograms the metabolism of Ewing sarcoma cells via positive regulation of glutamine import and serine-glycine biosynthesis［J］.Molecular Carcinogenesis,2018,57(10):1342-1357.
［35］BAO L,FESTA F,FREET CS,et al.The human transient receptor potential melastatin 2 ion channel modulates ros through Nrf2［J］.Scientific Reports,2019,9(1):14132.
［36］ZHANG Y,STOVALL D,WAN M,et al.SOX7 target genes and their contribution to its tumor suppressive function［J］.International Journal of Molecular Sciences,2018,19(5):1451.
［37］WAN X,WANG C,HUANG Z,et al.Cisplatin inhibits SIRT3-deacetylation MTHFD2 to disturb cellular redox balance in colorectal cancer cell［J］.Cell Death & Disease,2020,11(8):649.
［38］ZHAO X,REN G.LncRNA taurine-upregulated gene 1 promotes cell proliferation by inhibiting microRNA-9 in MCF-7 cells［J］.Journal of Breast Cancer,2016,19(4):349.
［39］GU Y,SI J,XIAO X,et al.miR-92a inhibits proliferation and induces apoptosis by regulating methylenetetrahydrofolate dehydrogenase 2(MTHFD2) expression in acute myeloid leukemia［J］.Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics,2017,25(7):1069-1079.
［40］LI SM,ZHAO YQ,HAO YL,et al.Upregulation of miR-504-3p is associated with favorable prognosis of acute myeloid leukemia and may serve as a tumor suppressor by targeting MTHFD2［J］.Eur Rev Med Pharmacol Sci,2019,23(3):1203-1213.
［41］XU T,ZHANG K,SHI J,et al.MicroRNA-940 inhibits glioma progression by blocking mitochondrial folate metabolism through targeting of MTHFD2［J］.Am J Cancer Res,2019,9(2):250-269.
［42］YAN Y,ZHANG D,LEI T,et al.MicroRNA-33a-5p suppresses colorectal cancer cell growth by inhibiting MTHFD2［J］.Clinical and Experimental Pharmacology and Physiology,2019,46(10):928-936.
［43］TONG D,ZHANG J,WANG X,et al.MiR-22,regulated by MeCP2,suppresses gastric cancer cell proliferation by inducing a deficiency in endogenous S-adenosylmethionine［J］.Oncogenesis,2020,9(11):99.
［44］TEDESCHI PM,VAZQUEZ A,KERRIGAN JE,et al.Mitochondrial methylenetetrahydrofolate dehydrogenase(MTHFD2) overexpression is associated with tumor cell proliferation and is a novel target for drug development［J］.Molecular Cancer Research,2015,13(10):1361-1366.
［45］ZHAO LN,BJORKLUND M,CALDEZ MJ,et al.Therapeutic targeting of the mitochondrial one-carbon pathway:Perspectives,pitfalls,and potential［J］.Oncogene,2021,40(13):2339-2354.
［46］GUSTAFSSON R,JEMTH A,GUSTAFSSON NMS,et al.Crystal structure of the emerging cancer target MTHFD2 in complex with a substrate-based inhibitor［J］.Cancer Research,2017,77(4):937-948.
［47］ASAI A,KOSEKI J,KONNO M,et al.Drug discovery of anticancer drugs targeting methylenetetrahydrofolate dehydrogenase 2［J］.Heliyon,2018,4(12):e1021.
［48］KAWAI J,OTA M,OHKI H,et al.Structure-based design and synthesis of an isozyme-selective MTHFD2 inhibitor with a tricyclic coumarin scaffold［J］.ACS Medicinal Chemistry Letters,2019,10(6):893-898.
［49］KAWAI J,TOKI T,OTA M,et al.Discovery of a potent,selective,and orally available MTHFD2 inhibitor(DS18561882) with in vivo antitumor activity［J］.Journal of Medicinal Chemistry,2019,62(22):10204-10220.
［50］LEE L,PENG Y,CHANG H,et al.Xanthine derivatives reveal an allosteric binding site in methylenetetrahydrofolate dehydrogenase 2(MTHFD2)［J］.Journal of Medicinal Chemistry,2021,64(15):11288-11301.