综述

m6A修饰在脊髓损伤恢复中的研究进展

  • 张东旭 ,
  • 赵欣华 ,
  • 蒋焕莹 ,
  • 周立新 ,
  • 孙忠人 ,
  • 尹洪娜
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  • 黑龙江中医药大学附属第二医院针灸七科 (哈尔滨 150006 )

收稿日期: 2023-07-16

  网络出版日期: 2023-11-15

基金资助

国家自然科学基金面上项目(81873378)

Research progress of m6A modification in spinal cord injury recovery

  • Dongxu ZHANG ,
  • Xinhua ZHAO ,
  • Huanying JIANG ,
  • Lixin ZHOU ,
  • Zhongren SUN ,
  • Hongna. YIN
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  • Acupuncture and Moxibustion Department VII,the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150006,China

Received date: 2023-07-16

  Online published: 2023-11-15

摘要

脊髓损伤是一种严重的中枢神经系统疾病,常引发运动功能障碍,并伴有多种严重并发症,严重影响患者生存质量。N6-甲基腺苷是发生于腺苷N6位点上的甲基化修饰,又称m6A甲基化修饰,因其在神经系统疾病诊断和治疗中的巨大潜力而被广泛关注。m6A修饰由甲基转移酶催化,去甲基化酶去除,甲基识别蛋白识别,其相关调节蛋白能够通过多种途径影响脊髓损伤及其继发损伤的发生发展。目前为止,m6A修饰在脊髓损伤中的作用机制尚未完全阐明。本文主要对m6A甲基化修饰的基本功能,及其在脊髓损伤中的作用及机制进行综述。

本文引用格式

张东旭 , 赵欣华 , 蒋焕莹 , 周立新 , 孙忠人 , 尹洪娜 . m6A修饰在脊髓损伤恢复中的研究进展[J]. 实用医学杂志, 2023 , 39(20) : 2676 -2682 . DOI: 10.3969/j.issn.1006-5725.2023.20.021

Abstract

Spinal cord injury (SCI) is a serious disease of the central nervous system (CNS), which often leads to motor dysfunction and is associated with a variety of serious complications, seriously affecting the quality of life of patients. N6-methyladenosine (m6A) is a methylation modification that occurs at the N6 site of adenosine, also known as the m6A methylation modification, which is of great interest because of its great potential for diagnosis and treatment of neurological diseases. m6A modifications are catalyzed by methyltransferases, removed by demethylases, recognized by methyl-recognition proteins, and its associated regulatory proteins can affect the development of SCI and its secondary damage through various pathways. Up to now, the mechanism of m6A modification in SCI has not been fully elucidated. In this paper, we review the basic functions of m6A modification and its role and mechanism in SCI.

参考文献

1 GILBERT E A B , LAKSHMAN N , LAU K S K , et al . Regulating Endogenous Neural Stem Cell Act-ivation to Promote Spinal Cord Injury Repair [J]. Cells,2022, 11(5):846.
2 BIE F , WANG K , XU T , et al . The potential roles of circular RNAs as modulators in traumatic spinal cord injury [J]. Biomed Pharmacother, 2021,141:111826.
3 BONIZZATO M , JAMES N D , PIDPRUZHNYKOVA G , et al . Multi-pronged neuromodulation intervention engages the residual motor circuitry to facilitate walking in a rat model of spinal cord injury [J]. Nat Commun, 2021, 12(1):1925.
4 ZHANG T , ZHANG S W , ZHANG S Y , et al . m6A-express: uncovering complex and condition-specific m6A regulation of gene expression [J]. Nucleic Acids Res, 2021, 49(20):e116.
5 郭岩松,李思柔,李琳,等 . m6A修饰在胶质瘤中的研究进展[J]. 实用医学杂志,2023,39(13):1724-1728..
6 LIU D , FAN B , LI J , et al . N6-methyladenosine modification: A potential regulatory mechanism in spinal cord injury [J]. Front Cell Neurosci, 2022, 16:989637.
7 LI L , XU N , LIU J , et al . m6A Methylation in Cardiovascular Diseases: From Mechanisms to Therapeutic Potential [J]. Front Genet, 2022,13:908976.
8 TIAN M , MAO L , ZHANG L . Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries [J]. Front Cell Neurosci,2022, 16:1013450.
9 ZACCARA S , RIES R J , JAFFREY S R . Reading, writing and erasing mRNA methylation [J]. Nat Rev Mol Cell Biol, 2019, 20(10):608-624.
10 ZHAO W , QI X , LIU L , et al . Epigenetic Regulation of m6A Modifications in Human Cancer [J]. Mol Ther Nucleic Acids, 2020, 19:405-412.
11 XU Z , PENG B , CAI Y , et al . N6-methyladenosine RNA modification in cancer therapeutic resistance: Current status and perspectives [J]. Biochem Pharmacol, 2020, 182:114258.
12 ZENG C , HUANG W , LI Y , et al . Roles of METTL3 in cancer: mechanisms and therapeutic targeting [J]. J Hematol Oncol, 2020, 13(1):117.
13 OERUM S , MEYNIER V , CATALA M , et al . A comprehensive review of m6A/m6Am RNA methyltransferase structures [J]. Nucleic Acids Res,2021,49(13):7239-7255.
14 YANG Y , HUANG G , JIANG X , et al . Loss of Wtap results in cerebellar ataxia and degeneration of Purkinje cells [J]. J Genet Genomics, 2022,49(9):847-858.
15 AZZAM S K , ALSAFAR H , SAJINI A A . FTO m6A Demethylase in Obesity and Cancer: Implications and Underlying Molecular Mechanisms [J]. Int J Mol Sci,2022, 23(7):3800.
16 CHOKKALLA A K , JEONG S , MEHTA S L , et al . Cerebroprotective Role of N6-Met-hyladenosineDemethylase FTO (Fat Mass and Obesity-Associated Protein) After Experimental Stroke [J].Stroke, 2023, 54(1):245-254.
17 LIU Y , YUAN Q , XIE L . The AlkB Family of Fe (II)/Alpha-Ketoglutarate-Dependent Dioxygenases Modulates Embryogenesis through Epigenetic Regulation [J]. Curr Stem Cell Res Ther, 2018, 13(2):136-143.
18 COVELO MOLARES H , OBRDLIK A , PO?TULKOVá I , et al . The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features [J]. Nucleic Acids Res, 2021, 49(19):10895-10910.
19 HUANG J , SHAO Y , GU W . Function and clinical significance of N6-methyladenosine in digestive system tumours [J]. Exp Hematol Oncol,2021, 10(1):40.
20 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.
21 ORR M B , GENSEL J C . Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses [J]. Neurotherapeutics, 2018, 15(3):541-553.
22 ZHOU X , WAHANE S , FRIEDL M S , et al . Microglia and macrophages promote corralling, wound compaction and recovery after spinal cord injury via Plexin-B2 [J]. Nat Neuro Sci, 2020, 23(3):337-350.
23 LIU W , RONG Y , WANG J , et al . Exosome-shuttled miR-216a-5p from hypoxic prec-onditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization [J]. J Neuroinflammation, 2020, 17(1):47.
24 CHEN F , HU M , SHEN Y , et al . Isorhamnetin promotes functional recovery in rats with spinal cord injury by abating oxidative stress and modulating M2 macrophages/microglia polarization [J]. Eur J Pharmacol, 2021, 895:173878.
25 ZHOU H , XU Z , LIAO X , et al . Low Expression of YTH Domain-Containing 1 Promotes Microglial M1 Polarization by Reducing the Stability of Sirtuin 1 mRNA [J]. Front Cell Neuro Sci, 2021, 15:774305.
26 WEN L , SUN W , XIA D , et al . The m6A methyltransferase METTL3 promotes LPS induced microglia inflammation through TRAF6/NF-κB pathway [J]. Neuro Report, 2022, 33(6):243-251.
27 DING L , WU H , WANG Y , et al . m6A Reader Igf2bp1 Regulates the Inflammatory Responses of Microglia by Stabilizing Gbp11 and Cp mRNAs [J]. Front Immunol, 2022, 13:872252.
28 LI Q , WEN S , YE W , et al . The potential roles of m6A modification in regulating the inflammatory response in microglia [J]. J Neuroinflammation, 2021, 18(1):149.
29 WU J , WANG X , LI X . N6-methyladenosine methylation regulator FTO promotes oxidative stress and induces cell apoptosis in ovarian cancer [J]. Epigenomics, 2022, 14(23):1509-1522.
30 HUANG W , LIN M , YANG C , et al . Rat Bone Mesenchymal Stem Cell-Derived Exosomes Loaded with miR-494 Promoting Neurofilament Regeneration and Behavioral Function Recovery after Spinal Cord Injury [J]. Oxid Med Cell Longev, 2021, 2021:1634917.
31 LI X , AN P , HAN F , et al . Silencing of YTHDF1 Attenuates Cerebral Stroke by Inducing PTEN Degradation and Activating the PTEN/AKT/mTOR Pathway [J]. Mol Bio technol, 2023,65(5):822-832.
32 WANG C X , CUI G S , LIU X , et al . METTL3-mediated m6A modification is required for cerebellar development [J]. PLoS Biol, 2018, 16(6):e2004880.
33 MING Y , DENG Z , TIAN X , et al . m6A Methyltransferase METTL3 Reduces Hippocampal Neuron Apoptosis in a Mouse Model of Autism Through the MALAT1/SFRP2/Wnt/β-catenin Axis [J]. Psychiatry Investig, 2022, 19(10):771-787.
34 WANG H , YUAN J , DANG X , et al . Mettl14-mediated m6A modification modulates neuro-n apoptosis during the repair of spinal cord injury by regulating the transformation f-rompri-mir-375 to miR-375 [J]. Cell Biosci, 2021, 11(1):52.
35 YANG J , XIONG L L , WANG Y C , et al . Oligodendrocyte precursor cell transplantation promotes functional recovery following contusive spinal cord injury in rats and is associate-d with altered microRNA expression [J]. Mol Med Rep, 2018, 17(1):771-782.
36 WIRAKIAT W , PROMMAHOM A , DHARMASAROJA P . Inhibition of the antioxidant enzyme PR-DX1 activity promotes MPP+-induced death in differentiated SH-SY5Y cells and may i-mpair its colocalization with eEF1A2 [J]. Life Sci, 2020, 258:118227.
37 GAO G , DUAN Y , CHANG F , et al . METTL14 promotes apoptosis of spinal cord neurons by inducing EEF1A2 m6A methylation in spinal cord injury [J]. Cell Death Discov, 2022, 8(1):15.
38 VISMARA I , PAPA S , VENERUSO V , et al . Selective Modulation of A1 Astrocytes by Drug-Loaded Nano-Structured Gel in Spinal Cord Injury [J]. ACS Nano, 2020, 14(1):360-371.
39 ZHOU Z L , XIE H , TIAN X B , et al . Microglial depletion impairs glial scar formation and aggravates inflammation partly by inhibiting STAT3 phosphorylation in astrocytes after spinal cord injury [J]. Neural Regen Res, 2023, 18(6):1325-1331.
40 韦入菲,曾高峰 . 减少脊髓损伤后胶质瘢痕形成方法的研究进展[J]. 实用医学杂志,2020, 36(20):2876-2880.
41 TENG Y , LIU Z , CHEN X , et al . Conditional deficiency of m6A methyltransferase Mettl14 in substantia nigra alters dopaminergic neuron function [J]. J Cell Mol Med, 2021, 25(17):8567-8572.
42 HUANG R , ZHANG Y , BAI Y , et al . N6-Methyladenosine Modification of Fatty Acid Amide-Hydrolase Messenger RNA in Circular RNA STAG1-Regulated Astrocyte Dysfunction and Depressive-like Behaviors [J]. Biol Psychiatry, 2020, 88(5):392-404.
43 GE X , YE W , ZHU Y , et al . USP1/UAF1-Stabilized METTL3 Promotes Reactive Astrogliosis and Improves Functional Recovery after Spinal Cord Injury through m6A Modification of YAP1 mRNA [J]. J Neuro Sci, 2023, 43(9):1456-1474.
44 XING L , CAI Y , YANG T , et al . Epi transcriptomic m6A regulation following spinal cord in-jury [J]. J Neuro Sci Res, 2021, 99(3):843-857.
45 VARADARAJAN S G , HUNYARA J L , HAMILTON N R , et al . Central nervous system regeneration [J]. Cell, 2022, 185(1):77-94.
46 HOU Y , LIU X , GUO Y , et al . Strategies for Effective Neural Circuit Reconstruction After Spinal Cord Injury: Use of Stem Cells and Biomaterials [J]. World Neuro Surg, 2022, 161:82-89.
47 HUANG L , FU C , XIONG F , et al . Stem Cell Therapy for Spinal Cord Injury [J]. Cell Transplant, 2021, 30:963689721989266.
48 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.
49 YU J , SHE Y , YANG L , et al . The m6 A Readers YTHDF1 and YTHDF2 Synergistically Control Cerebellar Parallel Fiber Growth by Regulating Local Translation of the Key Wnt5a Signaling Components in Axons [J]. Adv Sci (Weinh), 2021, 8(22):e2101329.
50 ZHUANG M , LI X , ZHU J , et al . The m6A reader YTHDF1 regulates axon guidance thro-ugh translational control of Robo3.1 expression [J]. Nucleic Acids Res, 2019, 47(9):4765-4777.
51 YOUNOSSI-HARTENSTEIN A , JONES M , HARTENSTEIN V . Embryonic development of the nervous system of the temnocephalid flatworm Craspedella pedum [J]. J Comp Neurol, 2001, 434(1):56-68.
52 LI C , ZHAO J , QIN T , et al . Comprehensive analysis of m6A methylation modification in chronic spinal cord injury in mice [J]. J Orthop Res, 2023,41(6):1320-1334.
53 LEI C , WANG Q . The Progression of N6-methyladenosine Study and Its Role in Neuro-psychiatric Disorders [J]. Int J Mol Sci, 2022, 23(11):5922.
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