- 中国科学论文统计源期刊
- 中国科技核心期刊
- 美国化学文摘(CA)来源期刊
- 日本科学技术振兴机构数据库(JST)
临床输血与检验 ›› 2023, Vol. 25 ›› Issue (5): 706-720.DOI: 10.3969/j.issn.1671-2587.2023.05.022
• 综述 • 上一篇
郑思晴1, 王昊2
收稿日期:2023-08-21
出版日期:2023-10-20
发布日期:2023-11-20
通讯作者:
王昊,主要从事m6A修饰在肿瘤进展中的调控机制的研究,（E-mail）demo@ustc.edu.cn。
作者简介:郑思晴,主要从事m6A修饰在肿瘤进展中的调控机制的研究,（E-mail）1873390087@qq.com。
基金资助:ZHENG Siqing, WANG Hao
Received:2023-08-21
Online:2023-10-20
Published:2023-11-20
摘要： 近年来,癌症治疗取得了巨大进步,显著提高了临床疗效。然而,肿瘤耐药一直是影响癌症治疗效果的关键问题,其复杂的机制仍然难以捉摸。N6-甲基腺苷（m6A）修饰作为表观遗传学研究的热点,被认为是克服耐药的潜在靶点,受到越来越多的关注。作为最常见的RNA修饰方式,m6A参与了RNA剪接、核输出、翻译、稳定性等RNA代谢的各个环节。m6A甲基转移酶（writer）,去甲基化酶（eraser）和RNA结合蛋白（reader）这三类调控分子共同协调m6A修饰的动态和可逆过程。本文主要综述了m6A修饰在肿瘤化疗和靶向治疗耐药中的作用及调控机制,并探讨m6A修饰在克服肿瘤化疗耐药和优化癌症治疗方面的临床潜力,同时展望了m6A修饰的未来研究方向。
中图分类号:
郑思晴, 王昊. m6A修饰对于肿瘤在传统化疗和新型靶向治疗耐药中的作用研究进展*[J]. 临床输血与检验, 2023, 25(5): 706-720.
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.
| [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. |
| [1] | 郑瑞, 浦春. 外泌体在常见恶性肿瘤化疗耐药中的作用*[J]. 临床输血与检验, 2019, 21(6): 664-669. |
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