|Table of Contents|

Research progress of m6A methylation and programmed cell death of tumor cells

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

Issue:
2023 22
Page:
4245-4251
Research Field:
Publishing date:

Info

Title:
Research progress of m6A methylation and programmed cell death of tumor cells
Author(s):
TANG Yue1; CHAI Xin1; LI Ximeng1; GUAN Xutao2; WANG Tao2
1.Henan University of Traditional Chinese Medicine，Henan Zhengzhou 450000,China；2.The First Affiliated Hospital of Henan University of Traditional Chinese Medicine，Henan Zhengzhou 450000,China.
Keywords:
m6A methylation; programmed cell death; tumor cells; mRNA
PACS:
R730
DOI:
10.3969/j.issn.1672-4992.2023.22.029
Abstract:
N6-methyladenosine (m6A) is the most common internal RNA modification in eukaryotic cells and has received increasing attention in recent years.m6A plays a diverse role in organisms,and its mechanism of action may be related to the changes in the position of the m6A gene sequence.m6A modification affects post-transcriptional modification from multiple aspects and plays an important regulatory role in various pathophysiological processes of cells.Programmed cell death (PCD) of tumor cells includes apoptosis,pyroptosis,ferroptosis,necroptosisand autophagy.This article will review the research progress of m6A methylation and tumor cell programmed death,and introduce the role of m6A methylation in vivo,the correlation between m6A methylation and PCD,the relationship between m6A and tumor through PCD pathway,and m6A through the significance of PCD pathway as a target in the diagnosis and treatment of tumor.

References:

［1］CHEN KW,DEMARCO B,BROZ P.Beyond inflammasomes:emerging function of gasdermins during apoptosis and NETosis［J］.Embo J,2020,39(2):376-397.
［2］GAUTHERON J,GORES GJ,RODRIGUES CMP.Lytic cell death in metabolic liver disease［J］.J Hepatol,2020,73(2):394-408.
［3］ZHANG C,ZHANG M,GE S,et al.Reduced m6A modification predicts malignant phenotypes and augmented Wnt/PI3K-Akt signaling in gastric cancer［J］.Cancer Med,2019,8(10):4766-4781.
［4］ZHONG H,TANG HF,KAI Y.N6-methyladenine RNA modification (m(6)A):An emerging regulator of metabolic diseases［J］.Curr Drug Targets,2020,21(11):1056-1067.
［5］PINELLO N,SUN S,WONG JJ.Aberrant expression of enzymes regulating m(6)A mRNA methylation:implication in cancer［J］.Cancer Biol Med,2018,15(4):323-334.
［6］LAN Q,LIU PY,HAASE J,et al.The critical role of RNA m(6)A methylation in cancer［J］.Cancer Res,2019,79(7):1285-1292.
［7］PING XL,SUN BF,WANG L,et al.Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase［J］.Cell Res,2014,24(2):177-189.
［8］LIU L,WANG Y,WU J,et al.N(6)-methyladenosine:A potential breakthrough for human cancer［J］.Mol Ther Nucleic Acids,2020,19(4):804-813.
［9］SCHWARTZ S,MUMBACH MR,JOVANOVIC M,et al.Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5' sites［J］.Cell Rep,2014,8(1):284-296.
［10］AOYAMA T,YAMASHITA S,TOMITA K.Mechanistic insights into m6A modification of U6 snRNA by human METTL16［J］.Nucleic Acids Res,2020,48(9):5157-5168.
［11］GONG PJ,SHAO YC,YANG Y,et al.Analysis of N6-methyladenosine methyltransferase reveals METTL14 and ZC3H13 as tumor suppressor genes in breast cancer［J］.Front Oncol,2020,10(1):578-983.
［12］LIU ZX,LI LM,SUN HL,et al.Link between m6A modification and cancers［J］.Front Bioeng Biotechnol,2018,6(4):89-97.
［13］HU Y,WANG S,LIU J,et al.New sights in cancer:Component and function of N6-methyladenosine modification［J］.Biomed Pharmacother,2020,12(2):109-124.
［14］ALLIS CD,JENUWEIN T.The molecular hallmarks of epigenetic control［J］.Nat Rev Genet,2016,17(8):487-500.
［15］WANG T,KONG S,TAO M,et al.The potential role of RNA N6-methyladenosine in cancer progression［J］.Mol Cancer,2020,19(1):88-99.
［16］ZHAO W,QI X,LIU L,et al.Epigenetic regulation of m(6)A modifications in human cancer［J］.Mol Ther Nucleic Acids,2020,19(2):405-412.
［17］LEE Y,CHOE J,PARK OH,et al.Molecular mechanisms driving mRNA degradation by m(6)A modification［J］.Trends Genet,2020,36(3):177-188.
［18］YU J,CHEN M,HUANG H,et al.Dynamic m6A modification regulates local translation of mRNA in axons［J］.Nucleic Acids Res,2018,46(3):1412-1423.
［19］KASOWITZ SD,MA J,ANDERSON SJ,et al.Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development［J］.PLoS Genet,2018,14(5):1007-1032.
［20］HUANG XT,LI JH,ZHU XX,et al.HNRNPC impedes m(6)A-dependent anti-metastatic alternative splicing events in pancreatic ductal adenocarcinoma［J］.Cancer Lett,2021,51(8):196-206.
［21］ZHOU KI,SHI H,LYU R,et al.Regulation of Co-transcriptional pre-mRNA splicing by m(6)A through the low-complexity protein hnRNPG［J］.Mol Cell,2019,76(1):70-81.
［22］ROUNDTREE IA,LUO GZ,ZHANG Z,et al.YTHDC1 mediates nuclear export of N(6)-methyladenosine methylated mRNAs［J］.Elife,2017,6(3):11-23.
［23］PI J,WANG W,JI M,et al.YTHDF1 promotes gastric carcinogenesis by controlling translation of FZD7［J］.Cancer Res,2021,81(10):2651-2665.
［24］KRETSCHMER J,RAO H,HACKERT P,et al.The m(6)A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5'-3' exoribonuclease XRN1［J］.Rna,2018,24(10):1339-1350.
［25］SUN T,WU R,MING L.The role of m6A RNA methylation in cancer［J］.Biomed Pharmacother,2019,11(2):108-123.
［26］ALARCON CR,GOODARZI H,LEE H,et al.HNRNPA2B1 is a mediator of m(6)A-dependent nuclear RNA processing events［J］.Cell,2015,12(6):1299-1308.
［27］ZHANG J,BAI R,LI M,et al.Excessive miR-25-3p maturation via N(6)-methyladenosine stimulated by cigarette smoke promotes pancreatic cancer progression［J］.Nat Commun,2019,10(1):18-58.
［28］SHEN J,FENG XP,HU RB,et al.N-methyladenosine reader YTHDF2-mediated long noncoding RNA FENDRR degradation promotes cell proliferation in endometrioid endometrial carcinoma［J］.Lab Invest,2021,11(6):775-784.
［29］YANG Y,FAN X,MAO M,et al.Extensive translation of circular RNAs driven by N(6)-methyladenosine［J］.Cell Res,2017,27(5):626-641.
［30］PANNEERDOSS S,EEDUNURI VK,YADAV P,et al.Cross-talk among writers,readers,and erasers of m(6)A regulates cancer growth and progression［J］.Sci Adv,2018,4(10):82-93.
［31］BARBIERI I,TZELEPIS K,PANDOLFINI L,et al.Promoter-bound METTL3 maintains myeloid leukaemia by m(6)A-dependent translation control［J］.Nature,2017,12(3):126-131.
［32］CUI Q,SHI H,YE P,et al.m(6)A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells［J］.Cell Rep,2017,18(11):2622-2634.
［33］RUAN DY,LI T,WANG YN,et al.FTO downregulation mediated by hypoxia facilitates colorectal cancer metastasis［J］.Oncogene,2021,40(33):5168-5181.
［34］LIU L,LI H,HU D,et al.Insights into N6-methyladenosine and programmed cell death in cancer［J］.Mol Cancer,2022,21(1):32-52.
［35］CHEN J,WANG C,FEI W,et al.Epitranscriptomic m6A modification in the stem cell field and its effects on cell death and survival［J］.Am J Cancer Res,2019,9(4):752-764.
［36］ZHOU X,HAN J,ZHEN X,et al.Analysis of genetic alteration signatures and prognostic values of m6A regulatory genes in head and neck squamous cell carcinoma［J］.Front Oncol,2020,10(1):718-732.
［37］SUN T,WU Z,WANG X,et al.Correction to:LNC942 promoting METTL14-mediated m 6 A methylation in breast cancer cell proliferation and progression［J］.Oncogene,2022.41(11):16-27.
［38］NIU Y,LIN Z,WAN A,et al.RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3［J］.Mol Cancer,2019,18(1):46-62.
［39］VAN OPDENBOSCH N,LAMKANFI M.Caspases in cell death,inflammation,and disease［J］.Immunity,2019,50(6):1352-1364.
［40］DIAO MY,ZHU Y,YANG J,et al.Hypothermia protects neurons against ischemia/reperfusion-induced pyroptosis via m6A-mediated activation of PTEN and the PI3K/Akt/GSK-3β signaling pathway［J］.Brain Res Bull,2020,15(2):25-31.
［41］ZHA X,XI X,FAN X,et al.Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8［J］.Aging (Albany NY),2020,12(9):8137-8150.
［42］GUO M,YAN R,JI Q,et al.IFN regulatory factor-1 induced macrophage pyroptosis by modulating m6A modification of circ_0029589 in patients with acute coronary syndrome［J］.Int Immunopharmacol,2020,8(2):106-120.
［43］MOU Y,WANG J,WU J,et al.Ferroptosis,a new form of cell death:opportunities and challenges in cancer［J］.J Hematol Oncol,2019,12(1):34-52.
［44］SONG Z,JIA G,MA P,et al.Exosomal miR-4443 promotes cisplatin resistance in non-small cell lung carcinoma by regulating FSP1 m6A modification-mediated ferroptosis［J］.Life Sci,2021,27(6):119-139.
［45］MA L,ZHANG X,YU K,et al.Targeting SLC3A2 subunit of system X(C)(-) is essential for m(6)A reader YTHDC2 to be an endogenous ferroptosis inducer in lung adenocarcinoma［J］.Free Radic Biol Med,2021,16(8):25-43.
［46］SARCOGNATO S,JONG IEM,FABRIS L,et al.Necroptosis in cholangiocarcinoma［J］.Cells,2020,9(4):69-82.
［47］LAN H,LIU Y,LIU J,et al.Tumor-associated macrophages promote oxaliplatin resistance via METTL3-mediated m(6)A of TRAF5 and necroptosis in colorectal cancer［J］.Mol Pharm,2021,18(3):1026-1037.
［48］DEVIS-JAUREGUI L,ERITJA N,DAVIS ML,et al.Autophagy in the physiological endometrium and cancer［J］.Autophagy,2021,17(5):1077-1095.
［49］JIN S,ZHANG X,MIAO Y,et al.m(6)A RNA modification controls autophagy through upregulating ULK1 protein abundance［J］.Cell Res,2018,28(9):955-957.
［50］YANG S,WEI J,CUI YH,et al.m(6)A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade［J］.Nat Commun,2019,10(1):27-82.
［51］LI B,JIANG J,ASSARAF YG,et al.Surmounting cancer drug resistance:New insights from the perspective of N(6)-methyladenosine RNA modification［J］.Drug Resist Updat,2020,5(3):100-120.
［52］WANG Q,GENG W,GUO H,et al.Emerging role of RNA methyltransferase METTL3 in gastrointestinal cancer［J］.J Hematol Oncol,2020,13(1):57-72.
［53］WANG H,XU B,SHI J.N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2［J］.Gene,2020,12(2):144-176.
［54］LI Q,NI Y,ZHANG L,et al.HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation［J］.Signal Transduct Target Ther,2021,6(1):76-87.
［55］YAN F,AL-KALI A,ZHANG Z,et al.A dynamic N(6)-methyladenosine methylome regulates intrinsic and acquired resistance to tyrosine kinase inhibitors［J］.Cell Res,2018,28(11):1062-1076.
［56］GUO J,WU Y,DU J,et al.Deregulation of UBE2C-mediated autophagy repression aggravates NSCLC progression［J］.Oncogenesis,2018,7(6):49-72.
［57］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.
［58］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):152-173.
［59］ZHANG Z,ZHU H,HU J.CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129［J］.Cell Death Dis,2021,12(2):219-230.
［60］SUN T,WU Z,WANG X,et al.LNC942 promoting METTL14-mediated m(6)A methylation in breast cancer cell proliferation and progression［J］.Oncogene,2020,39(31):5358-5372.
［61］YUAN Y,YAN G,HE M,et al.ALKBH5 suppresses tumor progression via an m(6)A-dependent epigenetic silencing of pre-miR-181b-1/YAP signaling axis in osteosarcoma［J］.Cell Death Dis,2021,12(1):60-72.
［62］HE H,WU W,SUN Z,et al.MiR-4429 prevented gastric cancer progression through targeting METTL3 to inhibit m(6)A-caused stabilization of SEC62［J］.Biochem Biophys Res Commun,2019,517(4):581-587.
［63］NAREN D,YAN T,GONG Y,et al.High Wilms' tumor 1 associating protein expression predicts poor prognosis in acute myeloid leukemia and regulates m(6)A methylation of MYC mRNA［J］.J Cancer Res Clin Oncol,2021,147(1):33-47.
［64］LIU J,REN D,DU Z,et al.m(6)A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression［J］.Biochem Biophys Res Commun,2018,502(4):456-464.

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