|Table of Contents|

The role of m6A RNA methylation in tumor microenvironment and tumor metabolism

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

Issue:
2024 06
Page:
1148-1154
Research Field:
Publishing date:

Info

Title:
The role of m6A RNA methylation in tumor microenvironment and tumor metabolism
Author(s):
SHEN Junjie1CHEN Wenming2
1.Jining Medical University,Shandong Jining 272067,China;2.The First People's Hospital of Jining,Shandong Jining 272000,China.
Keywords:
m6A modificationtumormicroenvironmenttumor metabolismreview
PACS:
R730
DOI:
10.3969/j.issn.1672-4992.2024.06.030
Abstract:
Tumor microenvironment and tumor metabolism are indispensable components in the growth process of malignant tumors.In recent years,many studies have concluded that m6A methylation plays an important role in malignant tumors through various complex mechanisms.m6A is the most extensive internal modification of RNA in eukaryotic cells,and participates in RNA metabolism by affecting RNA processing,nuclear export,RNA translation and decay.This article reviews the role of m6A RNA methylation modification in tumor microenvironment and tumor metabolism related pathways,aiming to illustrate the importance of targeting m6A in tumorigenesis and development.

References:

[1] ANDERSON NM,SIMON MC.The tumor microenvironment[J].Curr Biol,2020,30(16):R921-R925.
[2] PARK JH,PYUN WY,PARK HW.Cancer metabolism:phenotype,signaling and therapeutic targets[J].Cells,2020,9(10):2308.
[3] CHEN XY,ZHANG J,ZHU JS.The role of m6A RNA methylation in human cancer[J].Mol Cancer,2019,18(1):103.
[4] SUN T,WU R,MING L.The role of m6A RNA methylation in cancer[J].Biomed Pharmacother,2019,112:108613.
[5] SONG P,TAYIER S,CAI Z,et al.RNA methylation in mammalian development and cancer[J].Cell Biol Toxicol,2021,37(6):811-831.
[6] QIN Y,LI L,LUO E,et al.Role of m6A RNA methylation in cardiovascular disease (Review)[J].Int J Mol Med,2020,46(6):1958-1972.
[7] ZHANG B,JIANG H,DONG Z,et al.The critical roles of m6A modification in metabolic abnormality and cardiovascular diseases[J].Genes Dis,2021,8(6):746-758.
[8] LAN Q,LIU PY,BELL JL,et al.The emerging roles of RNA m6A methylation and demethylation as critical regulators of tumorigenesis,drug sensitivity,and resistance[J].Cancer Res,2021,81(13):3431-3440.
[9] ZHOU H,YIN K,ZHANG Y,et al.The RNA m6A writer METTL14 in cancers:Roles,structures,and applications[J].Biochim Biophys Acta Rev Cancer,2021,1876(2):188609.
[10] WANG T,KONG S,TAO M,et al.The potential role of RNA N6-methyladenosine in cancer progression[J].Mol Cancer,2020,19(1):88.
[11] YUE Y,LIU J,CUI X,et al.VIRMA mediates preferential m6A mRNA methylation in 3' UTR and near stop codon and associates with alternative polyadenylation[J].Cell Discov,2018,4:10.
[12] BAWANKAR P,LENCE T,PAOLANTONI C,et al.Hakai is required for stabilization of core components of the m6A mRNA methylation machinery[J].Nat Commun,2021,12(1):3778.
[13] CHELMICKI T,ROGER E,TEISSANDIER A,et al.m6A RNA methylation regulates the fate of endogenous retroviruses[J].Nature,2021,591(7849):312-316.
[14] ZHANG M,BODI Z,MACKINNON K,et al.Two zinc finger proteins with functions in m6A writing interact with HAKAI[J].Nat Commun,2022,13(1):1127.
[15] SU R,DONG L,LI Y,et al.METTL16 exerts an m6A-independent function to facilitate translation and tumorigenesis[J].Nat Cell Biol,2022,24(2):205-216.
[16] ZUIDHOF HR,CALKHOVEN CF.Oncogenic and tumor-suppressive functions of the RNA demethylase FTO[J].Cancer Res,2022,82(12):2201-2212.
[17] YOU Y,FU Y,HUANG M,et al.Recent advances of m6A demethylases inhibitors and their biological functions in human diseases[J].Int J Mol Sci,2022,23(10):5815.
[18] AZZAM SK,ALSAFAR H,SAJINI AA.FTO m6A demethylase in obesity and cancer:implications and underlying molecular mechanisms[J].Int J Mol Sci,2022,23(7):3800.
[19] QU J,YAN H,HOU Y,et al.RNA demethylase ALKBH5 in cancer:from mechanisms to therapeutic potential[J].J Hematol Oncol,2022,15(1):8.
[20] CHANG H,YANG J,WANG Q,et al.Role of N6-methyladenosine modification in pathogenesis of ischemic stroke[J].Expert Rev Mol Diagn,2022,22(3):295-303.
[21] WANG S,GAO S,ZENG Y,et al.N6-methyladenosine reader YTHDF1 promotes ARHGEF2 translation and RhoA signaling in colorectal cancer[J].Gastroenterology,2022,162(4):1183-1196.
[22] XU Z,LV B,QIN Y,et al.Emerging roles and mechanism of m6A methylation in cardiometabolic diseases[J].Cells,2022,11(7):1101.
[23] ZHAO Y,ZHAO H,ZHANG D,et al.YTHDF3 facilitates eIF2AK2 and eIF3A recruitment on mRNAs to regulate translational processes in oxaliplatin-resistant colorectal cancer[J].ACS Chem Biol,2022,17(7):1778-1788.
[24] LAN Q,LIU PY,HAASE J,et al.The critical role of RNA m6A methylation in cancer[J].Cancer Res,2019,79(7):1285-1292.
[25] ZACCARA S,JAFFREY SR.A unified model for the function of YTHDF proteins in regulating m6A-modified mRNA[J].Cell,2020,181(7):1582-1595.
[26] LI S,QI Y,YU J,et al.Nuclear aurora kinase A switches m6A reader YTHDC1 to enhance an oncogenic RNA splicing of tumor suppressor RBM4[J].Signal Transduct Target Ther,2022,7(1):97.
[27] WIDAGDO J,ANGGONO V,WONG JJ.The multifaceted effects of YTHDC1-mediated nuclear m6A recognition[J].Trends Genet,2022,38(4):325-332.
[28] MA C,LIAO S,ZHU Z.Crystal structure of human YTHDC2 YTH domain[J].Biochem Biophys Res Commun,2019,518(4):678-684.
[29] TANG J,CHEN Z,WANG Q,et al.hnRNPA2B1 promotes colon cancer progression via the MAPK pathway[J].Front Genet,2021,12:666451.
[30] LIU H,LI D,SUN L,et al.Interaction of lncRNA MIR100HG with hnRNPA2B1 facilitates m6A-dependent stabilization of TCF7L2 mRNA and colorectal cancer progression[J].Mol Cancer,2022,21(1):74.
[31] PENG WZ,ZHAO J,LIU X,et al.hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression[J].Cancer Cell Int,2021,21(1):281.
[32] GAO LB,ZHU XL,SHI JX,et al.HnRNPA2B1 promotes the proliferation of breast cancer MCF-7 cells via the STAT3 pathway[J].J Cell Biochem,2021,122(3-4):472-484.
[33] QUAN W,LI J,LIU L,et al.Influence of N6-methyladenosine modification gene HNRNPC on cell phenotype in Parkinson's disease[J].Parkinsons Dis,2021,2021:9919129.
[34] ZHOU KI,SHI H,LYU R,et al.Regulation of co-transcriptional pre-mRNA splicing by m6A through the low-complexity protein hnRNPG[J].Mol Cell,2019,76(1):70-81.
[35] SUN CY,CAO D,DU BB,et al.The role of insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m6A readers in cancer[J].Int J Biol Sci,2022,18(7):2744-2758.
[36] DU QY,ZHU ZM,PEI DS.The biological function of IGF2BPs and their role in tumorigenesis[J].Invest New Drugs,2021,39(6):1682-1693.
[37] LI Y,ZHAO L,LI XF.Hypoxia and the tumor microenvironment[J].Technol Cancer Res Treat,2021,20:2091189104.
[38] DOWNS-CANNER SM,MEIER J,VINCENT BG,et al.B cell function in the tumor microenvironment[J].Annu Rev Immunol,2022,40:169-193.
[39] YU W,LEI Q,YANG L,et al.Contradictory roles of lipid metabolism in immune response within the tumor microenvironment[J].J Hematol Oncol,2021,14(1):187.
[40] ROMERO-LOPEZ M,TRINH AL,SOBRINO A,et al.Recapitulating the human tumor microenvironment:Colon tumor-derived extracellular matrix promotes angiogenesis and tumor cell growth[J].Biomaterials,2017,116:118-129.
[41] BIFFI G,TUVESON DA.Diversity and biology of cancer-associated fibroblasts[J].Physiol Rev,2021,101(1):147-176.
[42] CORN KC,WINDHAM MA,RAFAT M.Lipids in the tumor microenvironment:From cancer progression to treatment[J].Prog Lipid Res,2020,80:101055.
[43] ROIFE D,SARCAR B,FLEMING JB.Stellate cells in the tumor microenvironment[J].Adv Exp Med Biol,2020,1263:67-84.
[44] ZHAI Y,ZHENG L.m6A RNA methylation regulator-related signatures exhibit good prognosis prediction ability for head and neck squamous cell carcinoma[J].Sci Rep,2022,12(1):16358.
[45] WANG L,HUI H,AGRAWAL K,et al.m6A RNA methyltransferases METTL3/14 regulate immune responses to anti-PD-1 therapy[J].EMBO J,2020,39(20):e104514.
[46] SONG H,SONG J,CHENG M,et al.METTL3-mediated m6A RNA methylation promotes the anti-tumour immunity of natural killer cells[J].Nat Commun,2021,12(1):5522.
[47] LI Y,SU R,DENG X,et al.FTO in cancer:functions,molecular mechanisms,and therapeutic implications[J].Trends Cancer,2022,8(7):598-614.
[48] GU X,ZHANG Y,LI D,et al.N6-methyladenosine demethylase FTO promotes M1 and M2 macrophage activation[J].Cell Signal,2020,69:109553.
[49] MORAD G,HELMINK BA,SHARMA P,et al.Hallmarks of response,resistance,and toxicity to immune checkpoint blockade[J].Cell,2021,184(21):5309-5337.
[50] TSURUTA N,TSUCHIHASHI K,OHMURA H,et al.RNA N6-methyladenosine demethylase FTO regulates PD-L1 expression in colon cancer cells[J].Biochem Biophys Res Commun,2020,530(1):235-239.
[51] DONG F,QIN X,WANG B,et al.ALKBH5 facilitates hypoxia-induced paraspeckle assembly and IL8 secretion to generate an immunosuppressive tumor microenvironment[J].Cancer Res,2021,81(23):5876-5888.
[52] HAN D,LIU J,CHEN C,et al.Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in dendritic cells[J].Nature,2019,566(7743):270-274.
[53] HU J,QIU D,YU A,et al.YTHDF1 is a potential pan-cancer biomarker for prognosis and immunotherapy[J].Front Oncol,2021,11:607224.
[54] BAI X,WONG CC,PAN Y,et al.Loss of YTHDF1 in gastric tumors restores sensitivity to antitumor immunity by recruiting mature dendritic cells[J].J Immunother Cancer,2022,10(2):e003663.
[55] VAUPEL P,MULTHOFF G.Revisiting the Warburg effect:historical dogma versus current understanding[J].J Physiol,2021,599(6):1745-1757.
[56] XUE L,LI J,LIN Y,et al.m6A transferase METTL3-induced lncRNA ABHD11-AS1 promotes the Warburg effect of non-small-cell lung cancer[J].J Cell Physiol,2021,236(4):2649-2658.
[57] LU S,HAN L,HU X,et al.N6-methyladenosine reader IMP2 stabilizes the ZFAS1/OLA1 axis and activates the Warburg effect:implication in colorectal cancer[J].J Hematol Oncol,2021,14(1):188.
[58] WANG Q,GUO X,LI L,et al.N6-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification[J].Cell Death Dis,2020,11(10):911.
[59] YU H,ZHAO K,ZENG H,et al.N6-methyladenosine (m6A) methyltransferase WTAP accelerates the Warburg effect of gastric cancer through regulating HK2 stability[J].Biomed Pharmacother,2021,133:111075.
[60] YU H,YANG X,TANG J,et al.ALKBH5 inhibited cell proliferation and sensitized bladder cancer cells to cisplatin by m6A-CK2alpha-mediated glycolysis[J].Mol Ther Nucleic Acids,2021,23:27-41.
[61] YANG X,SHAO F,GUO D,et al.WNT/beta-catenin-suppressed FTO expression increases m6A of c-Myc mRNA to promote tumor cell glycolysis and tumorigenesis[J].Cell Death Dis,2021,12(5):462.
[62] BIAN X,LIU R,MENG Y,et al.Lipid metabolism and cancer[J].J Exp Med,2021,218(1):e20201606.
[63] YANG Y,CAI J,YANG X,et al.Dysregulated m6A modification promotes lipogenesis and development of non-alcoholic fatty liver disease and hepatocellular carcinoma[J].Mol Ther,2022,30(6):2342-2353.
[64] SUN D,ZHAO T,ZHANG Q,et al.Fat mass and obesity-associated protein regulates lipogenesis via m6A modification in fatty acid synthase mRNA[J].Cell Biol Int,2021,45(2):334-344.
[65] GUO H,WANG B,XU K,et al.m6A reader HNRNPA2B1 promotes esophageal cancer progression via up-regulation of ACLY and ACC1[J].Front Oncol,2020,10:553045.
[66] ENIAFE J,JIANG S.The functional roles of TCA cycle metabolites in cancer[J].Oncogene,2021,40(19):3351-3363.
[67] XIAO Y,THAKKAR KN,ZHAO H,et al.The m6A RNA demethylase FTO is a HIF-independent synthetic lethal partner with the VHL tumor suppressor[J].Proc Natl Acad Sci USA,2020,117(35):21441-21449.
[68] ZHU S,WANG JZ,CHEN D,et al.An oncopeptide regulates m6A recognition by the m6A reader IGF2BP1 and tumorigenesis[J].Nat Commun,2020,11(1):1685.
[69] LI H,ZHANG Y,GUO Y,et al.ALKBH1 promotes lung cancer by regulating m6A RNA demethylation[J].Biochem Pharmacol,2021,189:114284.
[70] COURTNEY KD,BEZWADA D,MASHIMO T,et al.Isotope tracing of human clear cell renal cell carcinomas demonstrates suppressed glucose oxidation in vivo[J].Cell Metab,2018,28(5):793-800.
[71] 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.
[72] ZHUANG C,ZHUANG C,LUO X,et al.N6-methyladenosine demethylase FTO suppresses clear cell renal cell carcinoma through a novel FTO-PGC-1alpha signalling axis[J].J Cell Mol Med,2019,23(3):2163-2173.
[73] LIU X,GONZALEZ G,DAI X,et al.Adenylate kinase 4 modulates the resistance of breast cancer cells to tamoxifen through an m6A-based epitranscriptomic mechanism[J].Mol Ther,2020,28(12):2593-2604.
[74] XU W,XIE S,CHEN X,et al.Effects of quercetin on the efficacy of various chemotherapeutic drugs in cervical cancer cells[J].Drug Des Devel Ther,2021,15:577-588.
[75] SUN K,DU Y,HOU Y,et al.Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m6A signaling[J].Theranostics,2021,11(12):5831-5846.
[76] DING N,YOU A,TIAN W,et al.Chidamide increases the sensitivity of non-small cell lung cancer to crizotinib by decreasing c-MET mRNA methylation[J].Int J Biol Sci,2020,16(14):2595-2611.
[77] CHEN WW,QI JW,HANG Y,et al.Simvastatin is beneficial to lung cancer progression by inducing METTL3-induced m6A modification on EZH2 mRNA[J].Eur Rev Med Pharmacol Sci,2020,24(8):4263-4270.
[78] PAN X,HONG X,LI S,et al.METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner[J].Exp Mol Med,2021,53(1):91-102.
[79] SHRIWAS O,PRIYADARSHINI M,SAMAL SK,et al.DDX3 modulates cisplatin resistance in OSCC through ALKBH5-mediated m6A-demethylation of FOXM1 and NANOG[J].Apoptosis,2020,25(3-4):233-246.

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山东省自然科学基金面上项目(编号:ZR2020MH207,ZR2020MH251)
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