Research progress on mechanisms of m<sup>6</sup>A RNA methylated modification regulating non⁃small cell lung cancer

HAN Yang; JIANG Jingjie; SANG Shuliu; GAN Shanshan; BI Ling; GONG Yabin

doi:10.16306/j.1008-861x.2023.04.010

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Research progress on mechanisms of m⁶A RNA methylated modification regulating non⁃small cell lung cancer

Review | 更新时间：2023-08-04

- Research progress on mechanisms of m⁶A RNA methylated modification regulating non⁃small cell lung cancer
- Academic Journal of Shanghai University of Traditional Chinese Medicine Vol. 37, Issue 4, Pages: 83-89(2023)
- 作者机构：
  
  1.上海中医药大学附属岳阳中西医结合医院肿瘤一科（上海　200437）
- 作者简介：
- 基金信息：
- DOI：10.16306/j.1008-861x.2023.04.010
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韩阳,姜靖洁,桑舒柳等.m⁶A RNA甲基化修饰调控非小细胞肺癌作用机制的研究进展[J].上海中医药大学学报,2023,37(04):83-89.

HAN Yang,JIANG Jingjie,SANG Shuliu,et al.Research progress on mechanisms of m⁶A RNA methylated modification regulating non⁃small cell lung cancer[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2023,37(04):83-89.
韩阳,姜靖洁,桑舒柳等.m⁶A RNA甲基化修饰调控非小细胞肺癌作用机制的研究进展[J].上海中医药大学学报,2023,37(04):83-89. DOI： 10.16306/j.1008-861x.2023.04.010.

HAN Yang,JIANG Jingjie,SANG Shuliu,et al.Research progress on mechanisms of m⁶A RNA methylated modification regulating non⁃small cell lung cancer[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2023,37(04):83-89. DOI： 10.16306/j.1008-861x.2023.04.010.

摘要

N,6,-甲基腺苷（m,6,A）修饰是真核细胞RNA中普遍存在的一种动态可逆的化学修饰，可以调控各种RNA（包括lncRNA、mRNA、snRNA、rRNA和tRNA）的剪切、代谢、翻译和稳定性等。m,6,A能促进肿瘤细胞的生长增殖，并对放疗及化疗产生一定的抵抗作用，故以m,6,A为靶点进行靶向治疗可能成为一种新的癌症治疗方法。通过综述m,6,A RNA甲基化修饰参与非小细胞肺癌（NSCLC）的增殖、侵袭和转移、耐药、不良预后，以及中医药通过调控m,6,A RNA甲基化修饰抑制NSCLC等，为NSCLC的发病机制探讨及临床治疗提供新的理论依据和应对策略。

Abstract

N,6,-methyladenosine （m,6,A） modification is a dynamic and reversible chemical modification found commonly in the RNA of eukaryotic cells， which can regulate the splicing， metabolism， translation and stability of various RNAs （including lncRNA， mRNA， snRNA， rRNA and tRNA）. m,6,A can promote the growth and proliferation of tumor cells and exert a certain resistance to radiotherapy and chemotherapy， therefore， m,6,A as a target for cancer therapy may be a new therapeutic approach. This paper reviews the roles of m,6,A RNA methylated modification in the proliferation， invasion and metastasis， drug resistance， and poor prognosis of non-small cell lung cancer （NSCLC）， as well as the inhibition of NSCLC by Chinese medicine through regulating m,6,A RNA methylated modification， in order to provide the new theoretical basis and response strategies for the pathogenesis exploration and clinical treatment of NSCLC.

关键词

m6A RNA甲基化修饰非小细胞肺癌肿瘤增殖靶向耐药中药干预综述

Keywords

m6A RNA methylated modificationnon-small cell lung cancertumor proliferationtargeted drug resistanceChinese medicine interventionreview

references

SUNG H， FERLAY J， SIEGEL R L， et al. Global Cancer Statistics 2020： GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries ［J］. CA Cancer J Clin， 2021， 71（3）： 209-249.

MILLER K D， NOGUEIRA L， DEVASIA T， et al. Cancer treatment and survivorship statistics， 2022 ［J］. CA Cancer J Clin， 2022， 72（5）： 409-436.

袁婷，莫碧文. m6A-RNA甲基化在非小细胞肺癌中的研究进展［J］. 中国癌症防治杂志， 2020， 12（6）： 710-714.

YUAN T， MO B W. Research progress of m6A-RNA methylation in non-small cell lung cancer ［J］. Chinese Journal of Oncology Prevention and Treatment， 2020， 12（6）： 710-714.

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.

CSEPANY T， LIN A， JrBALDICK C J， et al. Sequence specificity of mRNA N6-adenosine methyltransferase ［J］. J Biol Chem， 1990， 265（33）： 20117-20122.

WU R， JIANG D， WANG Y， et al. N6-Methyladenosine （m6A） Methylation in mRNA with A Dynamic and Reversible Epigenetic Modification ［J］. Mol Biotechnol， 2016， 58（7）： 450-459.

REICHEL M， KÖSTER T， STAIGER D. Marking RNA： m6A writers， readers， and functions in Arabidopsis ［J］. J Mol Cell Biol， 2019， 11（10）： 899-910.

KIERZEK E， KIERZEK R. The thermodynamic stability of RNA duplexes and hairpins containing N6-alkyladenosines and 2-methylthio-N6-alkyladenosines ［J］. Nucleic Acids Res， 2003， 31（15）： 4472-4480.

LIU Z X， LI L M， SUN H L， et al. Link Between m6A Modification and Cancers ［J］. Front Bioeng Biotechnol， 2018， 6： 89.

CHEN C， GUO Y， GUO Y， et al. m6A Modification in Non-Coding RNA： The Role in Cancer Drug Resistance ［J］. Front Oncol， 2021， 11： 746789.

HUANG H， WENG H， CHEN J. m6A Modification in Coding and Non-coding RNAs： Roles and Therapeutic Implications in Cancer ［J］. Cancer Cell， 2020， 37（3）： 270-288.

JIANG X， LIU B， NIE Z， et al. The role of m6A modification in the biological functions and diseases ［J］. Signal Transduct Target Ther， 2021， 6（1）： 74.

SHEN S， ZHANG R， JIANG Y， et al. Comprehensive analyses of m6A regulators and interactive coding and non-coding RNAs across 32 cancer types ［J］. Mol Cancer， 2021， 20（1）： 67.

CHEN X Y， ZHANG J， ZHU J S. The role of m6A RNA methylation in human cancer ［J］. Mol Cancer， 2019， 18（1）： 103.

TAKETO K， KONNO M， ASAI A， et al. The epitranscriptome m6A writer METTL3 promotes chemo- and radioresistance in pancreatic cancer cells ［J］. Int J Oncol， 2018， 52（2）： 621-629.

WANG P， DOXTADER K A， NAM Y. Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases ［J］. Mol Cell， 2016， 63（2）： 306-317.

ZHANG Y， LIU S， ZHAO T， et al. METTL3-mediated m6A modification of Bcl-2 mRNA promotes non-small cell lung cancer progression ［J］. Oncol Rep， 2021， 46（2）： 163.

DU Y， HOU G， ZHANG H， et al. SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function ［J］. Nucleic Acids Res， 2018， 46（10）： 5195-5208.

JIN D， GUO J， WU Y， et al. m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC ［J］. Mol Cancer， 2020， 19（1）： 40.

ZHENG G， DAHL J A， NIU Y， et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility ［J］. Mol Cell， 2013， 49（1）： 18-29.

LUO S， TONG L. Molecular basis for the recognition of methylated adenines in RNA by the eukaryotic YTH domain ［J］. Proc Natl Acad Sci U S A， 2014， 111（38）： 13834-13839.

THELER D， DOMINGUEZ C， BLATTER M， et al. Solution structure of the YTH domain in complex with N6-methyladenosine RNA： a reader of methylated RNA ［J］. Nucleic Acids Res， 2014， 42（22）： 13911-13919.

XU C， LIU K， AHMED H， et al. Structural Basis for the Discriminative Recognition of N6-Methyladenosine RNA by the Human YT521-B Homology Domain Family of Proteins ［J］. J Biol Chem， 2015， 290（41）： 24902-24913.

XU C， WANG X， LIU K， et al. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain ［J］. Nat Chem Biol， 2014， 10（11）： 927-929.

SHI Y， FAN S， WU M， et al. YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression ［J］. Nat Commun， 2019， 10（1）： 4892.

SHENG H， LI Z， SU S， et al. YTH domain family 2 promotes lung cancer cell growth by facilitating 6-phosphogluconate dehydrogenase mRNA translation ［J］. Carcinogenesis， 2020， 41（5）： 541-550.

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 ［J］. Mol Cancer， 2021， 20（1）： 105.

LI B， ZHU L， LU C， et al. circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity ［J］. Nat Commun， 2021， 12（1）： 295.

HUANG H， WENG H， SUN W， et al. Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation ［J］. Nat Cell Biol， 2018， 20（3）： 285-295.

WU B， SU S， PATIL D P， et al. Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1 ［J］. Nat Commun， 2018， 9（1）： 420.

ZAPPA C， MOUSA S A. Non-small cell lung cancer： current treatment and future advances ［J］. Transl Lung Cancer Res， 2016， 5（3）： 288-300.

XU Y， CHEN Y， YAO Y， et al. VIRMA contributes to non-small cell lung cancer progression via N6-methyladenosine-dependent DAPK3 post-transcriptional modification ［J］. Cancer Lett， 2021， 522： 142-154.

LIU J， REN D， DU Z， et al. m6A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression ［J］. Biochem Biophys Res Commun， 2018， 502（4）： 456-464.

SUN Z， SU Z， ZHOU Z， et al. RNA demethylase ALKBH5 inhibits TGF-β-induced EMT by regulating TGF-β/SMAD signaling in non-small cell lung cancer ［J］. FASEB J， 2022， 36（5）： e22283.

ZHOU B， HAN Z. Crystallization and preliminary X-ray diffraction of the RNA demethylase ALKBH5 ［J］. Acta Crystallogr Sect F Struct Biol Cryst Commun， 2013， 69（Pt 11）： 1231-1234.

HU Y， GONG C， LI Z， et al. Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification ［J］. Mol Cancer， 2022， 21（1）： 34.

JIN D， GUO J， WU Y， et al. m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis ［J］. J Hematol Oncol， 2019， 12（1）： 135.

LIU S， LI Q， LI G， 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.

LI A， CHEN Y S， PING X L， et al. Cytoplasmic m6A reader YTHDF3 promotes mRNA translation ［J］. Cell Res， 2017， 27（3）： 444-447.

LIU X， MA C， LIU H， et al. M6A regulator expression patterns predict the immune microenvironment and prognosis of non-small cell lung cancer ［J］. J Cancer Res Clin Oncol， 2022， 148（10）： 2803-2814.

LEE Y， CHOE J， PARK O H， et al. Molecular Mechanisms Driving mRNA Degradation by m6A Modification ［J］. Trends Genet， 2020， 36（3）： 177-188.

PATIL D P， CHEN C K， PICKERING B F， et al. m6A RNA methylation promotes XIST-mediated transcriptional repression ［J］. Nature， 2016， 537（7620）： 369-373.

LI Y， ZHAO H， WANG Y， et al. Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer ［J］. Toxicol Appl Pharmacol， 2013， 272（1）： 37-48.

LEE C K， SON S H， PARK K K， et al. Isoliquiritigenin inhibits tumor growth and protects the kidney and liver against chemotherapy-induced toxicity in a mouse xenograft model of colon carcinoma ［J］. J Pharmacol Sci， 2008， 106（3）： 444-451.

ZHENG H， LI Y， WANG Y， et al. Downregulation of COX-2 and CYP 4A signaling by isoliquiritigenin inhibits human breast cancer metastasis through preventing anoikis resistance， migration and invasion ［J］. Toxicol Appl Pharmacol， 2014， 280（1）： 10-20.

CHEN C， HUANG S， CHEN C L， et al. Isoliquiritigenin Inhibits Ovarian Cancer Metastasis by Reversing Epithelial-to-Mesenchymal Transition ［J］. Molecules， 2019， 24（20）： 3725.

WANG J R， LUO Y H， PIAO X J， et al. Mechanisms underlying isoliquiritigenin-induced apoptosis and cell cycle arrest via ROS-mediated MAPK/STAT3/NF-κB pathways in human hepatocellular carcinoma cells ［J］. Drug Dev Res， 2019， 80（4）： 461-470.

JUNG S K， LEE M H， LIM D Y， et al. Isoliquiritigenin induces apoptosis and inhibits xenograft tumor growth of human lung cancer cells by targeting both wild type and L858R/T790M mutant EGFR ［J］. J Biol Chem， 2014， 289（52）： 35839-35848.

ZHOU J X， WINK M. Reversal of Multidrug Resistance in Human Colon Cancer and Human Leukemia Cells by Three Plant Extracts and Their Major Secondary Metabolites ［J］. Medicines （Basel）， 2018， 5（4）： 123.

CUI Y， WU Y， WANG C， et al. Isoliquiritigenin inhibits non-small cell lung cancer progression via m6A/IGF2BP3-dependent TWIST1 mRNA stabilization ［J］. Phytomedicine， 2022， 104： 154299.

HU C， YANG L， WANG Y， et al. Ginsenoside Rh2 reduces m6A RNA methylation in cancer via the KIF26B-SRF positive feedback loop ［J］. J Ginseng Res， 2021， 45（6）： 734-743.

XIAO H， XUE Q， ZHANG Q， et al. How Ginsenosides Trigger Apoptosis in Human Lung Adenocarcinoma Cells ［J］. Am J Chin Med， 2019， 47（8）： 1737-1754.

ZHU L M， SHI H X， SUGIMOTO M， et al. Feiyanning Formula Induces Apoptosis of Lung Adenocarcinoma Cells by Activating the Mitochondrial Pathway ［J］. Front Oncol， 2021， 11： 690878.

WU X， XIA J， WANG Z， et al. Feiyanning downregulating CXCLs/CXCR2 axis to suppress TANs infiltration in the prevention of lung cancer metastasis ［J］. J Ethnopharmacol， 2022， 295： 115277.

SANG S， SUN C， DING R， et al. Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway ［J］. Front Pharmacol， 2022， 13： 1019451.

张琦君，邓海滨，车勇，等. 肺岩宁方对Lewis荷瘤小鼠肿瘤相关性巨噬细胞极化的调控作用研究［J］. 中医药导报， 2021， 27（4）： 1-4， 19.

ZHANG Q J， DENG H B， CHE Y， et al. Study on the Regulating Effect of Feiyanning Prescription on the Polarization of Tumor-associated Macrophages in Lewis Tumor-bearing Mice［J］. Guiding Journal of Traditional Chinese Medicine and Pharmacy， 2021， 27（4）： 1-4， 19.

康小红，王颖，崔艳慧，等. 肺岩宁方调控MALAT1抑制A549肺癌细胞侵袭的机制研究［J］. 上海中医药杂志， 2019， 53（3）： 77-82.

KANG X H， WANG Y， CUI Y H， et al. Mechanism study on Feiyanning Recipe inhibiting invasion of A549 lung cancer cells by regulating MALAT1 ［J］. Shanghai Journal of Traditional Chinese Medicine， 2019， 53（3）： 77-82.

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Research progress on mechanisms of m6A RNA methylated modification regulating non⁃small cell lung cancer

DOI：10.16306/j.1008-861x.2023.04.010

摘要

Abstract

关键词

Keywords

references

Research progress on mechanisms of m⁶A RNA methylated modification regulating non⁃small cell lung cancer