|Table of Contents|

Research progress on the role of m6A reader protein YTHDF2 in tumors

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 02
Page:
344-350
Research Field:
Publishing date:

Info

Title:
Research progress on the role of m6A reader protein YTHDF2 in tumors
Author(s):
YANG Jie12LI Xiaoqin3YANG Yanli4ZHU Meng1LIU Zhe1MA Linna1LI Yaling1SHE Yali1
1.School of Basic Medicine,Gansu University of Chinese Medicine,Gansu Lanzhou 730000,China;2.Engineering Research Center of Molecular Pathological Diagnosis Technology of Gansu Province,Gansu Lanzhou 730000,China;3.Department of Pathology,Gansu Provincial Cancer Hospital,Gansu Lanzhou 730050,China;4.Department of Pathology,the 940th Hospital of Joint Logistics Support Force of People's Liberation Army,Gansu Lanzhou 730050,China.
Keywords:
m6A modificationYT521-B homology domain family proteins 2 (YTHDF2)tumormechanism
PACS:
R730
DOI:
10.3969/j.issn.1672-4992.2024.02.027
Abstract:
N6-methyladenosine (m6A) modification is one of the most common types of RNA modifications in eukaryotes and plays a key role in a variety of physiological processes and disease progression.YT521-B homology domain family proteins 2 (YTHDF2) is one of the important binding proteins of m6A modification,affecting the translation and stability of mRNAs.Studies have confirmed that YTHDF2 is involved in the development of various malignant tumors such as lung cancer,liver cancer,acute myeloid leukemia,etc.This article summarizes the regulatory mechanism of YTHDF2 in tumor development,and provides new ideas for anti-tumor research and development based on YTHDF2.

References:

[1] HUANG H,WENG H,CHEN J.M(6)A modification in coding and non-coding RNAs:roles and therapeutic implications in cancer[J].Cancer Cell,2020,37(3):270-288.
[2] LI F,ZHAO D,WU J,et al.Structure of the YTH domain of human YTHDF2 in complex with an m(6)A mononucleotide reveals an aromatic cage for m(6)A recognition[J].Cell Res,2014,24(12):1490-1492.
[3] ROIGNANT JY,SOLLER M.M(6)A in mRNA:an ancient mechanism for fine-tuning gene expression[J].Trends Genet,2017,33(6):380-390.
[4] PAN Y,MA P,LIU Y,et al.Multiple functions of m(6)A RNA methylation in cancer[J].J Hematol Oncol,2018,11(1):48.
[5] DOMINISSINI D,MOSHITCH-MOSHKOVITZ S,SCHWARTZ S,et al.Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq[J].Nature,2012,485(7397):201-206.
[6] WANG Y,LI Y,TOTH JI,et al.N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells[J].Nat Cell Biol,2014,16(2):191-198.
[7] MEYER KD,JAFFREY SR.Rethinking m(6)A readers,writers,and erasers[J].Annu Rev Cell Dev Biol,2017,33:319-342.
[8] DU H,ZHAO Y,HE J,et al.YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex[J].Nat Commun,2016,7:12626.
[9] PARIS J,MORGAN M,CAMPOS J,et al.Targeting the RNA m(6)A reader YTHDF2 selectively compromises cancer stem cells in acute myeloid leukemia[J].Cell Stem Cell,2019,25(1):137-148.
[10] CHEN Z,SHAO YL,WANG LL,et al.YTHDF2 is a potential target of AML1/ETO-HIF1alpha loop-mediated cell proliferation in t(8;21) AML[J].Oncogene,2021,40(22):3786-3798.
[11] ZACCARA S,RIES RJ,JAFFREY SR.Reading,writing and erasing mRNA methylation[J].Nat Rev Mol Cell Biol,2019,20(10):608-624.
[12] HARTMANN AM,NAYLER O,SCHWAIGER FW,et al.The interaction and colocalization of Sam68 with the splicing-associated factor YT521-B in nuclear dots is regulated by the Src family kinase p59(fyn)[J].Mol Biol Cell,1999,10(11):3909-3926.
[13] WANG X,LU Z,GOMEZ A,et al.N6-methyladenosine-dependent regulation of messenger RNA stability[J].Nature,2014,505(7481):117-120.
[14] WOJTAS MN,PANDEY RR,MENDEL M,et al.Regulation of m(6)A transcripts by the 3'-->5' RNA helicase YTHDC2 is essential for a successful meiotic program in the mammalian germline[J].Mol Cell,2017,68(2):374-387.
[15] DHOTE V,SWEENEY TR,KIM N,et al.Roles of individual domains in the function of DHX29,an essential factor required for translation of structured mammalian mRNAs[J].Proc Natl Acad Sci USA,2012,109(46):3150-3159.
[16] WANG X,ZHAO BS,ROUNDTREE IA,et al.N(6)-methyladenosine modulates messenger RNA translation efficiency[J].Cell,2015,161(6):1388-1399.
[17] CARDELLI M,MARCHEGIANI F,CAVALLONE L,et al.A polymorphism of the YTHDF2 gene (1p35) located in an Alu-rich genomic domain is associated with human longevity[J].J Gerontol A Biol Sci Med Sci,2006,61(6):547-556.
[18] WANG JY,LU AQ.The biological function of m6A reader YTHDF2 and its role in human disease[J].Cancer Cell Int,2021,21(1):109.
[19] XU P,HU K,ZHANG P,et al.Hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT axis[J].Cancer Cell Int,2022,22(1):13.
[20] ZHANG C,HUANG S,ZHUANG H,et al.YTHDF2 promotes the liver cancer stem cell phenotype and cancer metastasis by regulating OCT4 expression via m6A RNA methylation[J].Oncogene,2020,39(23):4507-4518.
[21] HOU J,ZHANG H,LIU J,et al.YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma[J].Mol Cancer,2019,18(1):163.
[22] XU F,LI J,NI M,et al.FBW7 suppresses ovarian cancer development by targeting the N(6)-methyladenosine binding protein YTHDF2[J].Mol Cancer,2021,20(1):45.
[23] SHENG H,LI Z,SU S,et al.YTH domain family 2 promotes lung cancer cell growth by facilitating 6-phosphogluconate dehydrogenase mRNA translation[J].Carcinogenesis,2020,41(5):541-550.
[24] LI Y,SHENG H,MA F,et al.RNA m(6)A reader YTHDF2 facilitates lung adenocarcinoma cell proliferation and metastasis by targeting the AXIN1/Wnt/beta-catenin signaling[J].Cell Death Dis,2021,12(5):479.
[25] ZHAO T,WANG M,ZHAO X,et al.YTHDF2 inhibits the migration and invasion of lung adenocarcinoma by negatively regulating the FAM83D-TGFbeta1-SMAD2/3 pathway[J].Front Oncol,2022,12:763341.
[26] EINSTEIN JM,PERELIS M,CHAIM IA,et al.Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer[J].Mol Cell,2021,81(15):3048-3064.
[27] ZHONG L,LIAO D,ZHANG M,et al.YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma[J].Cancer Lett,2019,442:252-261.
[28] 张杰,皮静楠,刘越,等.敲低MGC-803胃癌细胞YTHDF2抑制其增殖并促进其凋亡[J].细胞与分子免疫学杂志,2017,33(12):1628-1634. ZHANG J,PI JN,LIU Y,et al.Knockdown of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) inhibits proliferation and promotes apoptosis in MGC-803 gastric cancer cells[J].Chin J Cell Mol Imm,2017,33(12):1628-1634.
[29] SHEN X,ZHAO K,XU L,et al.YTHDF2 inhibits gastric cancer cell growth by regulating FOXC2 signaling pathway[J].Front Genet,2020,11:592042.
[30] LI H,ZHANG N,JIAO X,et al.Downregulation of microRNA-6125 promotes colorectal cancer growth through YTHDF2-dependent recognition of N6-methyladenosine-modified GSK3beta[J].Clin Transl Med,2021,11(10):e602.
[31] CHEN J,SUN Y,XU X,et al.YTH domain family 2 orchestrates epithelial-mesenchymal transition/proliferation dichotomy in pancreatic cancer cells[J].Cell Cycle,2017,16(23):2259-2271.
[32] TAN Z,SHI S,XU J,et al.RNA N6-methyladenosine demethylase FTO promotes pancreatic cancer progression by inducing the autocrine activity of PDGFC in an m(6)A-YTHDF2-dependent manner[J].Oncogene,2022,41(20):2860-2872.
[33] XIE H,LI J,YING Y,et al.METTL3/YTHDF2 m(6) A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer[J].J Cell Mol Med,2020,24(7):4092-4104.
[34] LI J,XIE H,YING Y,et al.YTHDF2 mediates the mRNA degradation of the tumor suppressors to induce AKT phosphorylation in N6-methyladenosine-dependent way in prostate cancer[J].Mol Cancer,2020,19(1):152.
[35] DU C,LV C,FENG Y,et al.Activation of the KDM5A/miRNA-495/YTHDF2/m6A-MOB3B axis facilitates prostate cancer progression[J].J Exp Clin Cancer Res,2020,39(1):223.
[36] HONG L,PU X,GAN H,et al.YTHDF2 inhibit the tumorigenicity of endometrial cancer via downregulating the expression of IRS1 methylated with m(6)A[J].J Cancer,2021,12(13):3809-3818.
[37] DIXIT D,PRAGER BC,GIMPLE RC,et al.The RNA m6A reader YTHDF2 maintains oncogene expression and is a targetable dependency in glioblastoma stem cells[J].Cancer Discov,2021,11(2):480-499.
[38] FANG R,CHEN X,ZHANG S,et al.EGFR/SRC/ERK-stabilized YTHDF2 promotes cholesterol dysregulation and invasive growth of glioblastoma[J].Nat Commun,2021,12(1):177.
[39] CHAI RC,CHANG YZ,CHANG X,et al.YTHDF2 facilitates UBXN1 mRNA decay by recognizing METTL3-mediated m(6)A modification to activate NF-kappaB and promote the malignant progression of glioma[J].J Hematol Oncol,2021,14(1):109.
[40] 刁新峰,李新茂,候亮,等.YTHDF2通过诱导IGFBP7的mRNA衰变激活PI3K/AKT信号转导通路促进胶质母细胞瘤进展的研究[J].中国癌症杂志,2022,32(03):218-227. DIAO XF,LI XM,HOU L,et al.YTHDF2 promotes progression of glioblastoma via inducing mRNA decay of IGFBP7 and activating PI3K/AKT signaling pathway[J].China Oncology,2022,32(03):218-227.
[41] YU J,CHAI P,XIE M,et al.Histone lactylation drives oncogenesis by facilitating m(6)A reader protein YTHDF2 expression in ocular melanoma[J].Genome Biol,2021,22(1):85.
[42] HUA Z,WEI R,GUO M,et al.YTHDF2 promotes multiple myeloma cell proliferation via STAT5A/MAP2K2/p-ERK axis[J].Oncogene,2022,41(10):1482-1491.
[43] WHITTAKER S,MARAIS R,ZHU AX.The role of signaling pathways in the development and treatment of hepatocellular carcinoma[J].Oncogene,2010,29(36):4989-5005.
[44] KOMPOSCH K,SIBILIA M.EGFR signaling in liver diseases[J].Int J Mol Sci,2015,17(1):30.
[45] NEUZILLET C,TIJERAS-RABALLAND A,DE MESTIER L,et al.MEK in cancer and cancer therapy[J].Pharmacol Ther,2014,141(2):160-171.
[46] SUN L,CHEN X,JIN X,et al.Identification and characterization of human MIBP1 gene in glioma cell differentiation[J].J Mol Neurosci,2014,52(2):294-301.
[47] YUAN JH,YANG F,WANG F,et al.A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma[J].Cancer Cell,2014,25(5):666-681.
[48] BOLLRATH J,PHESSE TJ,VON BURSTIN VA,et al.Gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis[J].Cancer Cell,2009,15(2):91-102.
[49] PIZZINGA M,HARVEY RF,RUBIO A,et al.Don't shoot the messenger...shoot the reader[J].Mol Cell,2021,81(15):3041-3042.
[50] THIERY JP,ACLOQUE H,HUANG RY,et al.Epithelial-mesenchymal transitions in development and disease[J].Cell,2009,139(5):871-890.
[51] LAMOUILLE S,XU J,DERYNCK R.Molecular mechanisms of epithelial-mesenchymal transition[J].Nat Rev Mol Cell Biol,2014,15(3):178-196.
[52] WANG J,XIANG H,LU Y,et al.Role and clinical significance of TGFbeta1 and TGFbetaR1 in malignant tumors (review)[J].Int J Mol Med,2021,47(4):55.
[53] MITTAL V.Epithelial mesenchymal transition in tumor metastasis[J].Annu Rev Pathol,2018,13:395-412.
[54] GOEL S,WONG AH,JAIN RK.Vascular normalization as a therapeutic strategy for malignant and nonmalignant disease[J].Cold Spring Harb Perspect Med,2012,2(3):a006486.
[55] WAGENBLAST E,SOTO M,GUTIERREZ-ANGEL S,et al.A model of breast cancer heterogeneity reveals vascular mimicry as a driver of metastasis[J].Nature,2015,520(7547):358-362.
[56] RANKIN EB,GIACCIA AJ.Hypoxic control of metastasis[J].Science,2016,352(6282):175-180.
[57] VALIENTE M,OBENAUF AC,JIN X,et al.Serpins promote cancer cell survival and vascular co-option in brain metastasis[J].Cell,2014,156(5):1002-1016.
[58] YAMINI B.NF-kappaB,mesenchymal differentiation and glioblastoma[J].Cells,2018,7(9):125.
[59] PLAKS V,KONG N,WERB Z.The cancer stem cell niche:how essential is the niche in regulating stemness of tumor cells[J].Cell Stem Cell,2015,16(3):225-238.
[60] LI Z,QIAN P,SHAO W,et al.Suppression of m(6)A reader Ythdf2 promotes hematopoietic stem cell expansion[J].Cell Res,2018,28(9):904-917.
[61] WANG H,ZUO H,LIU J,et al.Loss of YTHDF2-mediated m(6)A-dependent mRNA clearance facilitates hematopoietic stem cell regeneration[J].Cell Res,2018,28(10):1035-1038.
[62] MARTINEZ-REYES I,CHANDEL NS.Cancer metabolism:looking forward[J].Nat Rev Cancer,2021,21(10):669-680.
[63] HANAHAN D,WEINBERG RA.Hallmarks of cancer:the next generation[J].Cell,2011,144(5):646-674.
[64] ZHANG D,TANG Z,HUANG H,et al.Metabolic regulation of gene expression by histone lactylation[J].Nature,2019,574(7779):575-580.
[65] SARFRAZ I,RASUL A,HUSSAIN G,et al.6-Phosphogluconate dehydrogenase fuels multiple aspects of cancer cells:from cancer initiation to metastasis and chemoresistance[J].Biofactors,2020,46(4):550-562.
[66] WOOD T.Physiological functions of the pentose phosphate pathway[J].Cell Biochem Funct,1986,4(4):241-247.
[67] LIN R,ELF S,SHAN C,et al.6-Phosphogluconate dehydrogenase links oxidative PPP,lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling[J].Nat Cell Biol,2015,17(11):1484-1496.
[68] ZHENG W,FENG Q,LIU J,et al.Inhibition of 6-phosphogluconate dehydrogenase reverses cisplatin resistance in ovarian and lung cancer[J].Front Pharmacol,2017,8:421.
[69] 张梦雅,孙艳娣,骆严.磷酸戊糖途径重编程与肿瘤生长策略[J].生命的化学,2017,37(05):726-732. ZHANG MY,SUN YD,LUO Y.Pentose phosphate pathway reprogramming and tumorigenic strategy[J].Chemistry of Life,2017,37(05):726-732.
[70] HUANG B,SONG BL,XU C.Cholesterol metabolism in cancer:mechanisms and therapeutic opportunities[J].Nat Metab,2020,2(2):132-141.
[71] ZHANG J,LIU Q.Cholesterol metabolism and homeostasis in the brain[J].Protein Cell,2015,6(4):254-264.
[72] ZELCER N,HONG C,BOYADJIAN R,et al.LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor[J].Science,2009,325(5936):100-104.

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