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

Issue:

2024 08

Page:

1531-1537

Research Field:

Publishing date:

Info

Title:

Research progress on the role and mechanism of m6A RNA modification in drug resistance in non-small cell lung cancer treatment

Author(s):

LIU Sijian¹; QU Li¹; ZHANG Ling²; LIU Jiafeng²; YIN Wenjun²

1.Department of Clinical Laboratory Medicine,the First Affiliated Hospital,University of South China,Hunan Hengyang 421001£¬China£»2.Department of Clinical Laboratory Medicine,the Affiliated Changsha Central Hospital,University of South China,Hunan Hengyang 421004,China.

Keywords:

RNA methylation; non-small cell lung cancer; drug resistance

PACS:

R734.2

DOI:

10.3969/j.issn.1672-4992.2024.08.029

Abstract:

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors in the world.Although the treatment methods are constantly improving,drug resistance still restricts the treatment effect and patient prognosis.In recent years,studies have shown that N6-methyladenine (m6A) RNA modification plays a novel role in therapy resistance in NSCLC.m6A RNA modification is an important modification widely present in RNA molecules,which can regulate the stability,splicing,translation and localization of RNA,thereby affecting gene expression and cell function.This review will comprehensively analyze the new role of m6A RNA modification in NSCLC drug resistance and its underlying mechanism,in order to provide new strategies and methods for NSCLC treatment.

References:

£Û1£Ý MEYER KD,SALETORE Y,ZUMBO P,et al.Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons£ÛJ£Ý.Cell,2012,149(7):1635-1646.
£Û2£Ý HUANG H,WENG H,CHEN J.m6A modification in coding and non-coding RNAs:Roles and therapeutic implications in cancer£ÛJ£Ý.Cancer Cell,2020,37(3):270-288.
£Û3£Ý LAN Y,LIU B,GUO H.The role of m6A modification in the regulation of tumor-related lncRNAs£ÛJ£Ý.Molecular Therapy£ºNucleic Acids,2021,24:768-779.
£Û4£Ý DAI D,WANG H,ZHU L,et al.N6-methyladenosine links RNA metabolism to cancer progression£ÛJ£Ý.Cell Death & Disease,2018,9(2):124.
£Û5£Ý MILLER M,HANNA N.Advances in systemic therapy for non-small cell lung cancer£ÛJ£Ý.BMJ (Clinical Research Ed.),2021,375:n2363.
£Û6£Ý ETTINGER DS,WOOD DE,AISNER DL,et al.NCCN guidelines¡k insights:Non-small cell lung cancer,version 2.2023£ÛJ£Ý.Journal of the National Comprehensive Cancer Network,2023,21(4):340-350.
£Û7£Ý CHEN M,ZHANG Q,ZHENG S,et al.Cancer-associated fibroblasts promote migration and invasion of non-small cell lung cancer cells via METTL3-mediated RAC3 m6A modification£ÛJ£Ý.International Journal of Biological Sciences,2023,19(5):1616-1632.
£Û8£Ý MENG Q,WANG S,ZHOU S,et al.Dissecting the m6A methylation affection on afatinib resistance in non-small cell lung cancer£ÛJ£Ý.The Pharmacogenomics Journal,2020,20(2):227-234.
£Û9£Ý SHI L,GONG Y,ZHUO L,et al.Methyltransferase-like 3 upregulation is involved in the chemoresistance of non-small cell lung cancer£ÛJ£Ý.Annals of Translational Medicine,2022,10(3):139.
£Û10£Ý ZHANG S,SUN K,ZHENG R,et al.Cancer incidence and mortality in China,2015£ÛJ£Ý.Journal of the National Cancer Center,2021,1(1):2-11.
£Û11£Ý SIEGEL RL,MILLER KD,FUCHS HE,et al.Cancer statistics,2022£ÛJ£Ý.CA:A Cancer Journal for Clinicians,2022,72(1):7-33.
£Û12£Ý BENDER E.Epidemiology:The dominant malignancy£ÛJ£Ý.Nature,2014,513(7517):S2-3.
£Û13£Ý WANG N,CHEN W,ZHU W,et al.Incidence trends and pathological characteristics of lung cancer in urban Beijing during period of 1998-2007£ÛJ£Ý.Chinese Journal of Preventive Medicine,2011,45(3):249-254.
£Û14£Ý MIN HY,LEE HY.Mechanisms of resistance to chemotherapy in non-small cell lung cancer£ÛJ£Ý.Archives of Pharmacal Research,2021,44(2):146-164.
£Û15£Ý WU J,LIN Z.Non-small cell lung cancer targeted therapy:drugs and mechanisms of drug resistance£ÛJ£Ý.International Journal of Molecular Sciences,2022,23(23):15056.
£Û16£Ý SHARMA P,HU-LIESKOVAN S,WARGO JA,et al.Primary,adaptive,and acquired resistance to cancer immunotherapy£ÛJ£Ý.Cell,2017,168(4):707-723.
£Û17£Ý ÖлªÈËÃñ¹²ºÍ¹ú¹ú¼ÒÎÀÉú½¡¿µÎ¯Ô±»á.Ô­·¢ÐԷΰ©ÕïÁÆÖ¸ÄÏ£¨2022Äê°æ£©£ÛJ£Ý.ÖйúºÏÀíÓÃҩ̽Ë÷,2022,19(9):1-28. National Health Commission of the People's Republic of China.Guidelines for the diagnosis and treatment of primary lung cancer (2022 edition)£ÛJ£Ý.Exploration of Rational Drug Use in China,2022,19(9):1-28.
£Û18£Ý WANG X,FENG J,XUE Y,et al.Structural basis of N(6)-adenosine methylation by the METTL3-METTL14 complex£ÛJ£Ý.Nature,2016,534(7608):575-578.
£Û19£Ý JIANG X,LIU B,NIE Z,et al.The role of m6A modification in the biological functions and diseases£ÛJ£Ý.Signal Transduction and Targeted Therapy,2021,6(1):74.
£Û20£Ý ZHENG G,DAHL JA,NIU Y,et al.ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility£ÛJ£Ý.Molecular Cell,2013,49(1):18-29.
£Û21£Ý JIA G,FU Y,ZHAO X,et al.N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO£ÛJ£Ý.Nature Chemical Biology,2011,7(12):885-887.
£Û22£Ý QU J,YAN H,HOU Y,et al.RNA demethylase ALKBH5 in cancer:from mechanisms to therapeutic potential£ÛJ£Ý.Journal of Hematology & Oncology,2022,15(1):8.
£Û23£Ý WEI J,LIU F,LU Z,et al.Differential m6A,m6Am,and m1A demethylation mediated by FTO in the cell nucleus and cytoplasm£ÛJ£Ý.Molecular Cell,2018,71(6):973-985.
£Û24£Ý XIAO W,ADHIKARI S,DAHAL U,et al.Nuclear m(6)A reader YTHDC1 regulates mRNA splicing£ÛJ£Ý.Molecular Cell,2016,61(4):507-519.
£Û25£Ý ROUNDTREE IA,LUO GZ,ZHANG Z,et al.YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs£ÛJ£Ý.ELife,2017,6:e31311.
£Û26£Ý MAO Y,DONG L,LIU XM,et al.m6A in mRNA coding regions promotes translation via the RNA helicase-containing YTHDC2£ÛJ£Ý.Nature Communications,2019,10(1):5332.
£Û27£Ý OROUJI E,PEITSCH WK,OROUJI A,et al.Oncogenic role of an epigenetic reader of m6A RNA modification:YTHDF1 in merkel cell carcinoma£ÛJ£Ý.Cancers,2020,12(1):202.
£Û28£Ý HUANG H,WENG H,SUN W,et al.Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation£ÛJ£Ý.Nature Cell Biology,2018,20(3):285-295.
£Û29£Ý ZHOU KI,SHI H,LYU R,et al.Regulation of co-transcriptional pre-mRNA splicing by m6A through the low-complexity protein hnRNPG£ÛJ£Ý.Molecular Cell,2019,76(1):70-81.
£Û30£Ý BM EDENS,C VISSERS,J SU,et al.FMRP modulates neural differentiation through m6A-dependent mRNA nuclear export£ÛJ/OL£Ý.Cell Reports,2019,28(4)£Û2023-08-02£Ý.https://doi.org/10.1016/j.celrep.2019.06.072.
£Û31£Ý ROTTENBERG S,DISLER C,PEREGO P.The rediscovery of platinum-based cancer therapy£ÛJ£Ý.Nature Reviews Cancer,2021,21(1):37-50.
£Û32£Ý 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£ÛJ£Ý.Life Sciences,2021,276:119399.
£Û33£Ý 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£ÛJ£Ý.Journal of Cellular Physiology,2021,236(4):2649-2658.
£Û34£Ý LING Q,WU S,LIAO X,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-¦ÊB axis£ÛJ£Ý.BMC Cancer,2022,22(1):765.
£Û35£Ý SHI Y,FAN S,WU M,et al.YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression£ÛJ£Ý.Nature Communications,2019,10(1):4892.
£Û36£Ý ALDEA M,ANDRE F,MARABELLE A,et al.Overcoming resistance to tumor-targeted and immune-targeted therapies£ÛJ£Ý.Cancer Discovery,2021,11(4):874-899.
£Û37£Ý SIM EH,YANG IA,WOOD-BAKER R,et al.Gefitinib for advanced non-small cell lung cancer£ÛJ£Ý.The Cochrane Database of Systematic Reviews,2018,1(1):CD006847.
£Û38£Ý WU SG,SHIH JY.Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer£ÛJ£Ý.Molecular Cancer,2018,17(1):38.
£Û39£Ý ZHANG H,WANG SQ,WANG L,et al.m6A methyltransferase METTL3-induced lncRNA SNHG17 promotes lung adenocarcinoma gefitinib resistance by epigenetically repressing LATS2 expression£ÛJ£Ý.Cell Death & Disease,2022,13(7):657.
£Û40£Ý LIU S,LI Q,LI G,et al.The mechanism of m6A methyltransferase METTL3-mediated autophagy in reversing gefitinib resistance in NSCLC cells by ¦Â-elemene£ÛJ£Ý.Cell Death & Disease,2020,11(11):969.
£Û41£Ý DAI J,QU T,YIN D,et al.LncRNA LINC00969 promotes acquired gefitinib resistance by epigenetically suppressing of NLRP3 at transcriptional and posttranscriptional levels to inhibit pyroptosis in lung cancer£ÛJ£Ý.Cell Death & Disease,2023,14(5):312.
£Û42£Ý LIN X,YE R,LI Z,et al.KIAA1429 promotes tumorigenesis and gefitinib resistance in lung adenocarcinoma by activating the JNK/ MAPK pathway in an m6A-dependent manner£ÛJ£Ý.Drug Resistance Updates:Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy,2023,66:100908.
£Û43£Ý XIAO P,LIU YK,HAN W,et al.Exosomal delivery of FTO confers gefitinib resistance to recipient cells through ABCC10 regulation in an m6A-dependent manner£ÛJ£Ý.Molecular Cancer Research,2021,19(4):726-738.
£Û44£Ý CHEN H,JIA B,ZHANG Q,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£ÛJ£Ý.Frontiers in Oncology,2022,12:870636.
£Û45£Ý LIN Z,LI J,ZHANG J,et al.Metabolic reprogramming driven by IGF2BP3 promotes acquired resistance to EGFR inhibitors in non-small cell lung cancer£ÛJ£Ý.Cancer Research,2023,83(13):2187-2207.
£Û46£Ý LI K,PENG ZY,GAO S,et al.m6A associated TSUC7 inhibition contributed to Erlotinib resistance in lung adenocarcinoma through a Notch signaling activation dependent way£ÛJ£Ý.Journal of Experimental & Clinical Cancer Research,2021,40(1):325.
£Û47£Ý 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£ÛJ£Ý.Frontiers in Oncology,2021,11:731561.
£Û48£Ý 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£ÛJ£Ý.International Journal of Biological Sciences,2020,16(14):2595-2611.
£Û49£Ý LIU Z,WANG T,SHE Y,et al.N6-methyladenosine-modified circIGF2BP3 inhibits CD8+ T-cell responses to facilitate tumor immune evasion by promoting the deubiquitination of PD-L1 in non-small cell lung cancer£ÛJ£Ý.Molecular Cancer,2021,20(1):105.
£Û50£Ý WU L,CHENG D,YANG X,et al.M2-TAMs promote immunoresistance in lung adenocarcinoma by enhancing METTL3-mediated m6A methylation£ÛJ£Ý.Annals of Translational Medicine,2022,10(24):1380.
£Û51£Ý XIAO H,ZHAO R,MENG W,et al.Effects and translatomics characteristics of a small-molecule inhibitor of METTL3 against non-small cell lung cancer£ÛJ£Ý.Journal of Pharmaceutical Analysis,2023,13(6):625-639.
£Û52£Ý DOHOPOLSKI M,GOTTUMUKKALA S,GOMEZ D,et al.Radiation therapy in non-small-cell lung cancer£ÛJ£Ý.Cold Spring Harbor Perspectives in Medicine,2021,11(10):a037713.
£Û53£Ý XU X,ZHANG P,HUANG Y,et al.METTL3-mediated m6A mRNA contributes to the resistance of carbon-ion radiotherapy in non-small-cell lung cancer£ÛJ£Ý.Cancer Science,2023,114(1):105-114.
£Û54£Ý ABNER JJ,FRANKLIN JL,CLEMENT MA,et al.Depletion of METTL3 alters cellular and extracellular levels of miRNAs containing m6A consensus sequences£ÛJ£Ý.Heliyon,2021,7(12):e08519.

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