The Research Progress of m6A Modification on the Drug Resistance of Tumors in Traditional Chemotherapy and New Targeted Therapies

doi:10.3969/j.issn.1671-2587.2023.05.022

JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE ›› 2023, Vol. 25 ›› Issue (5): 706-720.DOI: 10.3969/j.issn.1671-2587.2023.05.022

The Research Progress of m6A Modification on the Drug Resistance of Tumors in Traditional Chemotherapy and New Targeted Therapies

ZHENG Siqing, WANG Hao

School of Pharmacy, Anhui Medical University, Hefei 230000

Received:2023-08-21 Online:2023-10-20 Published:2023-11-20

Abstract

Abstract: Objective Marvelous advancements have been made in cancer therapies to improve clinical outcomes over last few years. However, therapeutic resistance has always been a major difficulty in cancer therapy, with extremely complicated mechanisms remain elusive. N6-methyladenosine (m6A) RNA modification, a hotspot in epigenetics, has gained growing attention as a potential determinant of therapeutic resistance. As the most prevalent RNA modification, m6A is involved in every links of RNA metabolism, including RNA splicing, nuclear export, translation and stability. Three kinds of regulators, methyltransferase (writer), demethylase (eraser) and RNA binding proteins (reader), together orchestrate the dynamic and reversible process of m6A modification. Herein, we primarily reviewed the regulatory mechanisms of m6A in therapeutic resistance, including chemotherapy and targeted therapy. Then we discussed the clinical potential of m6A modification to overcome resistance and optimize cancer therapy. Additionally, we proposed prospects of m6A modification for future research.

Key words: Cancer therapy, m6A, Chemoresistance, Targeted therapy resistance

CLC Number:

R730.5

ZHENG Siqing, WANG Hao. The Research Progress of m6A Modification on the Drug Resistance of Tumors in Traditional Chemotherapy and New Targeted Therapies[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2023, 25(5): 706-720.

References

[1] MEYER K D,SALETORE Y,ZUMBO P,et al.Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons[J]. Cell,2012,149(7):1635-1646.
[2] ZHAO B S,ROUNDTREE I A,HE C.Post-transcriptional gene regulation by mRNA modifications[J]. Nat Rev Mol Cell Biol,2017,18(1):31-42.
[3] 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.
[4] HUANG H L,WENG H Y,CHEN J J. m⁶A modification in coding and non-coding RNAs:roles and therapeutic implications in cancer[J]. Cancer Cell,2020,37(3):270-288.
[5] XIAO W,ADHIKARI S,DAHAL U,et al.Nuclear m(6)a reader YTHDC1 regulates mRNA splicing[J]. Mol Cell,2016,61(4):507-519.
[6] MEYER K D,PATIL D P,ZHOU J,et al.5' UTR m(6)a promotes cap-independent translation[J]. Cell,2015,163(4):999-1010.
[7] LUO J Y,LIU H,LUAN S Y,et al.Aberrant regulation of mRNA m6A modification in cancer development[J]. Int J Mol Sci,2018,19(9):2515.
[8] DAI D J,WANG H Y,ZHU L Y,et al.N6-methyladenosi ne links RNA metabolism to cancer progression[J]. Cell Death Dis,2018,9(2):124.
[9] SIEGEL R L,MILLER K D,FUCHS H E,et al.Cancer statistics,2022[J]. CA A Cancer J Clinicians,2022,72(1):7-33.
[10] DAGOGO-JACK I,SHAW A T.Tumour heterogeneity and resistance to cancer therapies[J]. Nat Rev Clin Oncol,2018,15(2):81-94.
[11] ZHOU J B,KANG Y,CHEN L,et al.The drug-resistance mechanisms of five platinum-based antitumor agents[J]. Front Pharmacol,2020,11:343.
[12] LI H F,WANG C M,LAN L X,et al.METTL3 promotes oxaliplatin resistance of gastric cancer CD133+ stem cells by promoting PARP1 mRNA stability[J]. Cell Mol Life Sci,2022,79(3):135.
[13] CHEN H F,XIANG Y L,YIN Y H,et al.The m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting ATG5 in seminoma[J].Transl Androl Urol,2021,10:1711-1722.
[14] ZHANG R N,LI S W,LIU L J,et al.TRIM11 facilitates chemoresistance in nasopharyngeal carcinoma by activating the β-catenin/ABCC9 axis via p62-selective autophagic degradation of Daple[J]. Oncogenesis,2020,9(5):45.
[15] XU Z J,PENG B,CAI Y,et al.N6-methyladenosine RNA modification in cancer therapeutic resistance:current status and perspectives[J]. Biochem Pharmacol,2020,182:114258.
[16] LIU J Z,YUE Y N,HAN D L,et al.A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation[J]. Nat Chem Biol,2014,10(2):93-95.
[17] JIANG X L,LIU B Y,NIE Z,et al.The role of m6A modification in the biological functions and diseases[J]. Signal Transduct Target Ther,2021,6(1):74.
[18] JIA G F,FU Y,ZHAO X,et al.N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO[J]. Nat Chem Biol,2011,7(12):885-887.
[19] ZHENG G Q,DAHL J A,NIU Y M,et al.ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility[J]. Mol Cell,2013,49(1):18-29.
[20] BARTOSOVIC M,MOLARES H C,GREGOROVA P,et al.N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3'-end processing[J]. Nucleic Acids Res,2017,45(19):11356-11370.
[21] ZUIDHOF H R,CALKHOVEN C F.Oncogenic and tumor-suppressive functions of the RNA demethylase FTO[J]. Cancer Res,2022,82(12):2201-2212.
[22] TANG C,KLUKOVICH R,PENG H Y,et al.ALKBH5-dependent m6A demethylation controls splicing and stability of long 3'-UTR mRNAs in male germ cells[J]. Proc Natl Acad Sci USA,2018,115(2):E325-E333.
[23] ROUNDTREE I A,LUO G Z,ZHANG Z J,et al.YTHDC1 mediates nuclear export of N⁶-methyladenosine methylated mRNAs[J]. eLife,2017,6:e31311.
[24] SHIMA H,MATSUMOTO M,ISHIGAMI Y,et al.S-adenosylmethionine synthesis is regulated by selective N⁶-adenosine methylation and mRNA degradation involving METTL16 and YTHDC1[J]. Cell Rep,2017,21(12):3354-3363.
[25] WOJTAS M N,PANDEY R R,MENDEL M,et al. Regulation of m⁶A 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.e12.
[26] MAO Y H,DONG L M,LIU X M,et al.m⁶A in mRNA coding regions promotes translation via the RNA helicase-containing YTHDC2[J]. Nat Commun,2019,10(1):5332.
[27] OROUJI E,PEITSCH W K,OROUJI A,et al.Oncogenic role of an epigenetic reader of m⁶A RNA modification:YTHDF1 in merkel cell carcinoma[J]. Cancers,2020,12(1):202.
[28] SHI H L,WANG X A,LU Z K,et al.YTHDF3 facilitates translation and decay of N⁶-methyladenosine-modified RNA[J]. Cell Res,2017,27(3):315-328.
[29] HUANG H L,WENG H Y,SUN W J,et al.Publisher Correction:recognition of RNA N⁶-methyladenosine by IGF2BP proteins enhances mRNA stability and translation[J]. Nat Cell Biol,2020,22(10):1288.
[30] ZHOU K I,SHI H L,LYU R T,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.e9.
[31] EDENS B M,VISSERS C,SU J,et al. FMRP modulates neural differentiation through m⁶A-dependent mRNA nuclear export[J]. Cell Rep,2019,28(4):845-854.e5.
[32] CARCELES-CORDON M,KELLY W K,GOMELLA L,et al.Cellular rewiring in lethal prostate cancer:the architect of drug resistance[J]. Nat Rev Urol,2020,17(5):292-307.
[33] WHEATE N J,WALKER S,CRAIG G E,et al.The status of platinum anticancer drugs in the clinic and in clinical trials[J]. Dalton Trans,2010,39(35):8113-8127.
[34] SHI L,GONG Y X,ZHUO L,et al.Methyltransferase-like 3 upregulation is involved in the chemoresistance of non-small cell lung cancer[J]. Ann Transl Med,2022,10(3):139.
[35] LING Q,WU S Y,LIAO X Z,et al.Anesthetic propofol enhances cisplatin-sensitivity of non-small cell lung cancer cells through N6-methyladenosine-dependently regulating the miR-486-5p/RAP1-NF-κB axis[J]. BMC Cancer,2022,22(1):765.
[36] SONG Z Y,JIA G,MA P Z,et al.Exosomal miR-4443 promotes cisplatin resistance in non-small cell lung carcinoma by regulating FSP1 m6A modification-mediated ferroptosis[J]. Life Sci,2021,276:119399.
[37] ZHU L Y,ZHU Y R,HAN S T,et al.Impaired autophagic degradation of lncRNA ARHGAP5-AS1 promotes chemoresistance in gastric cancer[J]. Cell Death Dis,2019,10(6):383.
[38] YANG H,HU Y R,WENG M Z,et al.Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer[J]. J Adv Res,2022,37:91-106.
[39] ZHU Y R,ZHOU B L,HU X Y,et al.LncRNA LINC00942 promotes chemoresistance in gastric cancer by suppressing MSI2 degradation to enhance c-Myc mRNA stability[J]. Clin Transl Med,2022,12(1):e703.
[40] SUN T,WU Z K,WANG X F,et al.LNC942 promoting METTL14-mediated m⁶A methylation in breast cancer cell proliferation and progression[J]. Oncogene,2020,39(31):5358-5372.
[41] ZHANG Y,KANG M,ZHANG B,et al.m⁶A modification-mediated CBX8 induction regulates stemness and chemosensitivity of colon cancer via upregulation of LGR5[J]. Mol Cancer,2019,18(1):185.
[42] LAN H R,LIU Y Y,LIU J L,et al.Tumor-associated macrophages promote oxaliplatin resistance via METTL3-mediated m⁶A of TRAF₅ and necroptosis in colorectal cancer[J]. Mol Pharm,2021,18(3):1026-1037.
[43] CHEN P,LIU X Q,LIN X,et al.Targeting YTHDF1 effectively re-sensitizes cisplatin-resistant colon cancer cells by modulating GLS-mediated glutamine metabolism[J]. Mol Ther Oncolytics,2021,20:228-239.
[44] NIE S,ZHANG L,LIU J H,et al.ALKBH5-HOXA10 loop-mediated JAK2 m6A demethylation and cisplatin resistance in epithelial ovarian cancer[J].J Exp Clin Cancer Res,2021,1:284.
[45] HAO L,WANG J M,LIU B Q,et al.m6A-YTHDF1-mediated TRIM29 upregulation facilitates the stem cell-like phenotype of cisplatin-resistant ovarian cancer cells[J].Biochim Biophys Acta Mol Cell Res,2021,1868(1):118878.
[46] CHEN X,ZHANG J T,RUAN W M,et al.Urine DNA methylation assay enables early detection and recurrence monitoring for bladder cancer[J]. J Clin Invest,2020,130(12):6278-6289.
[47] TONG S M,WANG Y,WU J,et al.Comprehensive pharmacogenomics characterization of temozolomide response in gliomas[J]. Eur J Pharmacol,2021,912:174580.
[48] SHI J A,CHEN G,DONG X C,et al.METTL3 promotes the resistance of glioma to temozolomide via increasing MGMT and ANPG in a m6A dependent manner[J]. Front Oncol,2021,11:702983.
[49] LI X D,WANG M J,ZHENG J L,et al.Long noncoding RNA just proximal to X-inactive specific transcript facilitates aerobic glycolysis and temozolomide chemoresistance by promoting stability of PDK1 mRNA in an m6A-dependent manner in glioblastoma multiforme cells[J]. Cancer Sci,2021,112(11):4543-4552.
[50] SU R,DONG L,LI C Y,et al. R-2HG exhibits anti-tumor activity by targeting FTO/m6A/MYC/CEBPA signaling[J]. Cell,2018,172(1/2):90-105.e23.
[51] DING C Y,YI X H,CHEN X R,et al.Warburg effect-promoted exosomal circ_0072083 releasing up-regulates NANGO expression through multiple pathways and enhances temozolomide resistance in glioma[J]. J Exp Clin Cancer Res,2021,40(1):164.
[52] HEINEMANN V.Gemcitabine:progress in the treatment of pancreatic cancer[J]. Oncology,2000,60(1):8-18.
[53] YE X,WANG L P,HAN C,et al.Increased m6A modification of lncRNA DBH-AS1 suppresses pancreatic cancer growth and gemcitabine resistance via the miR-3163/USP44 axis[J]. Ann Transl Med,2022,10(6):304.
[54] ZHANG C J,OU S Y,ZHOU Y,et al.m⁶A methyltransferase METTL14-mediated upregulation of cytidine deaminase promoting gemcitabine resistance in pancreatic Cancer[J]. Front Oncol,2021,11:696371.
[55] NOORDHUIS P,HOLWERDA U,VAN DER WILT C L,et al. 5-Fluorouracil incorporation into RNA and DNA in relation to thymidylate synthase inhibition of human colorectal cancers[J]. Ann Oncol,2004,15(7):1025-1032.
[56] BUDACH V.TPF sequential therapy:when and for whom?[J]. Oncol,2010,15(S3):13-18.
[57] VODENKOVA S,BUCHLER T,CERVENA K,et al.5-fluorouracil and other fluoropyrimidines in colorectal cancer:past,present and future[J]. Pharmacol Ther,2020,206:107447.
[58] PAN S L,DENG Y Y,FU J,et al.N6-methyladenosine upregulates miR-181d-5p in exosomes derived from cancer-associated fibroblasts to inhibit 5-FU sensitivity by targeting NCALD in colorectal cancer[J]. Int J Oncol,2022,60(2):14.
[59] MA Y N,HONG Y G,YU G Y,et al.LncRNA LBX2-AS1 promotes colorectal cancer progression and 5-fluorouracil resistance[J]. Cancer Cell Int,2021,21(1):501.
[60] LIN Z Y,WAN A H,SUN L,et al.N6-methyladenosine demethylase FTO enhances chemo-resistance in colorectal cancer through SIVA1-mediated apoptosis[J]. Mol Ther,2023,31(2):517-534.
[61] NISHIZAWA Y,KONNO M,ASAI A,et al.Oncogene c-Myc promotes epitranscriptome m⁶A reader YTHDF1 expression in colorectal cancer[J]. Oncotarget,2018,9(7):7476-7486.
[62] JIANG Z P,HOU Z H,LIU W,et al.Circular RNA protein tyrosine kinase 2 (circPTK2) promotes colorectal cancer proliferation,migration,invasion and chemoresistance[J]. Bioengineered,2022,13(1):810-823.
[63] TEWEY K M,ROWE T C,YANG L,et al.Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II[J]. Science,1984,226(4673):466-468.
[64] TOKARSKA-SCHLATTNER M,ZAUGG M,ZUPPINGER C,et al.New insights into doxorubicin-induced cardiotoxicity:the critical role of cellular energetics[J]. J Mol Cell Cardiol,2006,41(3):389-405.
[65] LI S M,JIANG F R,CHEN F Y,et al.Effect of m⁶A methyltransferase METTL3-mediated MALAT1/E2F1/AGR2 axis on adriamycin resistance in breast cancer[J]. J Biochem Mol Toxicol,2022,36(1): e22922.
[66] PAN X P,HONG X L,LI S M,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.
[67] CHEN Z J,WU L,ZHOU J W,et al.N⁶-methyladenosine-induced ERRγ triggers chemoresistance of cancer cells through upregulation of ABCB1 and metabolic reprogramming[J]. Theranostics,2020,10(8):3382-3396.
[68] WANG X,HE S B,GU Y T,et al.Fatty acid receptor GPR120 promotes breast cancer chemoresistance by upregulating ABC transporters expression and fatty acid synthesis[J]. EBioMedicine,2019,40:251-262.
[69] HUANG T,CAO L L,FENG N N,et al.N⁶-methyladenosine (m⁶A)-mediated lncRNA DLGAP1-AS1enhances breast canceradriamycin resistance through miR-299-3p/WTAP feedback loop[J]. Bioengineered,2021,12(2):10935-10944.
[70] WANG Y,CHENG Z Q,XU J,et al.Fat mass and obesity-associated protein (FTO) mediates signal transducer and activator of transcription 3 (STAT3)-drived resistance of breast cancer to doxorubicin[J]. Bioengineered,2021,12(1):1874-1889.
[71] YANG Z,ZHAO F,GU X,et al.Binding of RNA m6A by IGF₂BP₃ triggers chemoresistance of HCT8 cells via upregulation of ABCB1[J]. Am J Cancer Res,2021,11(4):1428-1445.
[72] ZHOU C L,ZHANG Z C,ZHU X S,et al.N6-Methyladenosine modification of the TRIM7 positively regulates tumorigenesis and chemoresistance in osteosarcoma through ubiquitination of BRMS1[J]. eBioMedicine,2020,59:102955.
[73] LAI X,WEI J A,GU X Z,et al.Dysregulation of LINC00470 and METTL3 promotes chemoresistance and suppresses autophagy of chronic myelocytic leukaemia cells[J]. J Cellular Molecular Medi,2021,25(9):4248-4259.
[74] WANG Z, HE J, BACH DH, et al.Induction of m(6)A methylation in adipocyte exosomal LncRNAs mediates myeloma drug resistance[J].J Exp Clin Cancer Res,2022,41(1):4.
[75] WANG A R,CHEN Y F,SHI L Y,et al.Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce Arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis[J]. J Transl Med,2022,20(1):288.
[76] PAN Z P,WANG B,HOU D Y,et al.METTL3 mediates bone marrow mesenchymal stem cell adipogenesis to promote chemoresistance in acute myeloid leukaemia[J]. FEBS Open Bio,2021,11(6):1659-1672.
[77] WANG D, SUN Z, ZHU X, et al.GARP-mediated active TGF-β1 induces bone marrow NK cell dysfunction in AML patients with early relapse post-allo-HSCT[J]. Blood,2022,140(26):2788-2804.
[78] LIU J,ZHU J,WANG X,et al.A novel YTHDF3-based model to predict prognosis and therapeutic response in breast cancer[J].Front Mol Biosci,2022,874532.
[79] ZHANG Z H,ZHANG C Q,YANG Z Y,et al.m⁶A regulators as predictive biomarkers for chemotherapy benefit and potential therapeutic targets for overcoming chemotherapy resistance in small-cell lung cancer[J]. J Hematol Oncol,2021,14(1):190.
[80] ALDEA M,ANDRE F,MARABELLE A,et al.Overcoming resistance to tumor-targeted and immune-targeted therapies[J]. Cancer Discov,2021,11(4):874-899.
[81] WILHELM S M,CARTER C,TANG L Y,et al.BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis[J]. Cancer Res,2004,64(19):7099-7109.
[82] LLOVET J M,RICCI S,MAZZAFERRO V,et al.Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med,2008,359(4):378-390.
[83] LIU Z F,LU J,FANG H,et al.m6A modification-mediated DUXAP8 regulation of malignant phenotype and chemotherapy resistance of hepatocellular carcinoma through miR-584-5p/MAPK1/ERK pathway axis[J]. Front Cell Dev Biol,2021,9:783385.
[84] CHEN Y T,XIANG D,ZHAO X Y,et al.Upregulation of lncRNA NIFK-AS1 in hepatocellular carcinoma by m⁶A methylation promotes disease progression and sorafenib resistance[J]. Hum Cell,2021,34(6):1800-1811.
[85] XU J J,WAN Z,TANG M Y,et al.N⁶-methyladenosine-modified CircRNA-SORE sustains sorafenib resistance in hepatocellular carcinoma by regulating β-catenin signaling[J]. Mol Cancer,2020,19(1):163.
[86] LIN Z Y,NIU Y,WAN A,et al.RNA m⁶A methylation regulates sorafenib resistance in liver cancer through FOXO3- mediated autophagy[J]. EMBO J,2020,39(12):e103181.
[87] ZHOU T F,LI S C,XIANG D M,et al.m⁶A RNA methylation-mediated HNF₃γ reduction renders hepatocellular carcinoma dedifferentiation and sorafenib resistance[J]. Sig Transduct Target Ther,2020,5:296.
[88] TAN C Z,XIA P,ZHANG H,et al.YY1-targeted RBM15B promotes hepatocellular carcinoma cell proliferation and sorafenib resistance by promoting TRAM2 expression in an m6A-dependent manner[J]. Front Oncol,2022,12:873020.
[89] SIM E H,YANG I A,WOOD-BAKER R,et al. Gefitinib for advanced non-small cell lung cancer[J]. Cochrane Database Syst Rev,2018,1(1):CD006847.
[90] WU S G,SHIH J Y.Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer[J]. Mol Cancer,2018,17(1):38.
[91] ZHANG H,WANG S Q,WANG L,et al.m⁶A methyltransferase METTL3-induced lncRNA SNHG17 promotes lung adenocarcinoma gefitinib resistance by epigenetically repressing LATS2 expression[J]. Cell Death Dis,2022,13(7):657.
[92] LIU S P,LI Q J,LI G H,et al.The mechanism of m⁶A methyltransferase METTL3-mediated autophagy in reversing gefitinib resistance in NSCLC cells by β-elemene[J]. Cell Death Dis,2020,11(11):969.
[93] TANG J,HAN T C,TONG W,et al.N6-methyladenosine (m6A) methyltransferase KIAA1429 accelerates the gefitinib resistance of non-small-cell lung cancer[J]. Cell Death Discov,2021,7:108.
[94] LIN X,YE R Y,LI Z M,et al.KIAA1429 promotes tumorigenesis and gefitinib resistance in lung adenocarcinoma by activating the JNK/MAPK pathway in an m⁶A-dependent manner[J]. Drug Resist Updat,2023,66:100908.
[95] XIAO P,LIU Y K,HAN W,et al.Exosomal delivery of FTO confers gefitinib resistance to recipient cells through ABCC10 regulation in an m6A-dependent manner[J]. Mol Cancer Res,2021,19(4):726-738.
[96] HUI C,BIN J,QIANG Z,et al.Meclofenamic acid restores gefinitib sensitivity by downregulating breast cancer resistance protein and multidrug resistance protein 7 via FTO/m6A-demethylation/c-myc in non-small cell lung Cancer[J]. Front Oncol,2022,12:870636.
[97] LI K,PENG Z Y,GAO S,et al.M6A associated TSUC7 inhibition contributed to Erlotinib resistance in lung adenocarcinoma through a Notch signaling activation dependent way[J]. J Exp Clin Cancer Res,2021,40(1):1-14.
[98] LI K,GAO S,MA L,et al.Stimulation of let-7 maturation by metformin improved the response to tyrosine kinase inhibitor therapy in an m6A dependent manner[J]. Front Oncol,2022,11:731561.
[99] SCOTT L J.Apatinib:a review in advanced gastric cancer and other advanced cancers[J]. Drugs,2018,78(7):747-758.
[100] KE W W,ZHANG L L,ZHAO X X,et al.p53 m⁶A modulation sensitizes hepatocellular carcinoma to apatinib through apoptosis[J]. Apoptosis,2022,27(5/6):426-440.
[101] CHEN Y L,LU Z Y,QI C,et al.N⁶-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma[J]. Mol Cancer,2022,21(1):111.
[102] DING N,YOU A B,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.
[103] KONSTANTINOPOULOS P A,MATULONIS U A.PARP inhibitors in ovarian cancer:a trailblazing and transformative journey[J]. Clin Cancer Res,2018,24(17):4062-4065.
[104] FUKUMOTO T,ZHU H R,NACARELLI T,et al.N6-methylation of adenosine of FZD10 mRNA contributes to PARP inhibitor resistance[J].Cancer Res,2019,11:2812-2820.
[105] LAN Q,LIU P Y,BELL J L,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.
[106] SELBERG S,BLOKHINA D,AATONEN M,et al. Discovery of small molecules that activate RNA methylation through cooperative binding to the METTL3-14-WTAP complex active site[J]. Cell Rep,2019,26(13):3762-3771.e5.
[107] YANKOVA E,BLACKABY W,ALBERTELLA M,et al.Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia[J]. Nature,2021,593(7860):597-601.
[108] WENG H Y,HUANG F,YU Z J,et al. The m⁶A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia[J]. Cancer Cell,2022,40(12):1566-1582.e10.
[109] CHEN B E,YE F,YU L,et al.Development of cell-active N6-methyladenosine RNA demethylase FTO inhibitor[J]. J Am Chem Soc,2012,134(43):17963-17971.
[110] HUANG Y,YAN J L,LI Q,et al.Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5[J]. Nucleic Acids Res,2015,43(1):373-384.
[111] HUANG Y,SU R,SHENG Y,et al. Small-molecule targeting of oncogenic FTO demethylase in acute myeloid leukemia[J]. Cancer Cell,2019,35(4):677-691.e10.
[112] LIU Z Y,DUAN Z L,ZHANG D Y,et al.Structure-activity relationships and antileukemia effects of the tricyclic benzoic acid FTO inhibitors[J]. J Med Chem,2022,65(15):10638-10654.
[113] XIE G Y,WU X N,LING Y Y,et al.A novel inhibitor of N₆-methyladenosine demethylase FTO induces mRNA methylation and shows anti-cancer activities[J]. Acta Pharm Sin B,2022,12(2):853-866.
[114] HUFF S,KUMMETHA I R,ZHANG L Z,et al.Rational design and optimization of m⁶A-RNA demethylase FTO inhibitors as anticancer agents[J]. J Med Chem,2022,65(16):10920-10937.
[115] BINNEWIES M,ROBERTS E W,KERSTEN K,et al.Understanding the tumor immune microenvironment (TIME) for effective therapy[J]. Nat Med,2018,24(5):541-550.
[116] GU Y R,WU X,ZHANG J X,et al.The evolving landscape of N⁶-methyladenosine modification in the tumor microenvironment[J]. Mol Ther,2021,29(5):1703-1715.
[117] MORVAN M G,LANIER L L.NK cells and cancer:You can teach innate cells new tricks[J]. Nat Rev Cancer,2016,16(1):7-19.
[118] MA S B,YAN J Z,BARR T,et al.The RNA m6A reader YTHDF₂ controls NK cell antitumor and antiviral immunity[J]. J Exp Med,2021,218(8):e20210279.
[119] SUN Y Q,SHEN W T,HU S L,et al.METTL3 promotes chemoresistance in small cell lung cancer by inducing mitophagy[J]. J Exp Clin Cancer Res,2023,42(1):65.
[120] BEDI R K,HUANG D Z,EBERLE S A,et al.Small-molecule inhibitors of METTL3,the major human epitranscriptomic writer[J]. ChemMedChem,2020,15(9):744-748.
[121] MOROZ-OMORI E V,HUANG D Z,KUMAR BEDI R,et al. METTL3 inhibitors for epitranscriptomic modulation of cellular processes[J]. ChemMedChem,2021,16(19):3035-3043.
[122] DOLBOIS A,BEDI R K,BOCHENKOVA E,et al.1,4,9-triazaspiro[5.5]undecan-2-one derivatives as potent and selective METTL3 inhibitors[J]. J Med Chem,2021,64(17):12738-12760.
[123] ABNER J J,FRANKLIN J L,CLEMENT M A,et al.Depletion of METTL3 alters cellular and extracellular levels of miRNAs containing m⁶A consensus sequences[J]. Heliyon,2021,7(12):e08519.
[124] UDDIN M B,ROY K R,HOSAIN S B,et al.An N⁶-methyladenosine at the transited codon 273 of p53 pre-mRNA promotes the expression of R273H mutant protein and drug resistance of cancer cells[J]. Biochem Pharmacol,2019,160:134-145.

The Research Progress of m6A Modification on the Drug Resistance of Tumors in Traditional Chemotherapy and New Targeted Therapies

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 6

Recommended Articles

Metrics

Comments

About

Author

Journal

Access Statistics

Contact

[1]	QIANG Ping, XUE Lei, WANG Min, et al.. Successful Treatment of Cytokine Release Syndrome and CAR-T Cell-related Encephalopathy Syndrome: A Report of Two Cases and Literature Review [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2020, 22(4): 413-419.
[2]	. [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2019, 21(6): 664-669.
[3]	CHEN Yuan. Efficacy of Chemotherapy Combined with Endocrinotherapy in Patients with Luminal A Breast Cancer [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2019, 21(5): 517-520.
[4]	. [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2018, 20(1): 106-108.
[5]	TAN Jin-zhe, LIU Min-xue, TAN Bin. Analysis of the Efficacy of Red Blood Cell Suspension Infusion During Chemotherapy for Tumor Patients [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2017, 19(2): 129-131.
[6]	. [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2016, 18(4): 406-409.