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中华口腔医学研究杂志(电子版) ›› 2022, Vol. 16 ›› Issue (01) : 1 -6. doi: 10.3877/cma.j.issn.1674-1366.2022.01.001

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长链非编码RNA的m6A甲基化修饰在多种疾病中的调控作用
陈欣1, 刘佳1, 秦文1, 金作林1,()   
  1. 1. 军事口腔医学国家重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔疾病临床医学研究中心,第四军医大学口腔医院正畸科,西安 710032
  • 收稿日期:2022-01-12 出版日期:2022-02-01
  • 通信作者: 金作林

Research progress on the regulatory role of m6A methylation modification of long non-coding RNA in various diseases

Xin Chen1, Jia Liu1, Wen Qin1, Zuolin Jin1,()   

  1. 1. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China
  • Received:2022-01-12 Published:2022-02-01
  • Corresponding author: Zuolin Jin
  • Supported by:
    National Natural Science Foundation of China(81970960、82001079); Supporting Project for Key Talents of the Third Affiliated Hospital of Air Force Military Medical University(2020GGRC05)
引用本文:

陈欣, 刘佳, 秦文, 金作林. 长链非编码RNA的m6A甲基化修饰在多种疾病中的调控作用[J]. 中华口腔医学研究杂志(电子版), 2022, 16(01): 1-6.

Xin Chen, Jia Liu, Wen Qin, Zuolin Jin. Research progress on the regulatory role of m6A methylation modification of long non-coding RNA in various diseases[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2022, 16(01): 1-6.

随着高通量测序技术的发展,N6-甲基腺嘌呤(m6A)修饰作为表观遗传学修饰中最具代表性的一种修饰方式,广泛存在于多种生物大分子上,并且充分参与调控各种生物进程。长链非编码RNA(lncRNA)作为生命进程的调控者,参与调节了多种生理过程及疾病的发展。近期发现,部分lncRNA上存在m6A甲基化修饰,该修饰对lncRNA本身的结构和功能产生影响,从而对多种疾病产生不同的影响。本文就lncRNA的m6A甲基化修饰在多种疾病中的调控作用进行文献回顾,展望lncRNA的m6A修饰在口腔医学领域的应用和研究前景,以期对研究者们提供更好的研究思路。

With the development of high-throughput sequencing technology, N6-methyladenosine (m6A) , as one of the most representative epigenetic modifications, widely exists on a variety of biological macromolecules and is fully involved in the regulation of various biological processes. As a regulator of life process, long non-coding RNA (lncRNA) participates in the regulation of various physiological processes and the development of diseases. Recently, m6A methylation modification was found on some lncRNAs, which affected the structure and function of lncRNA itself, and had different effects on a variety of diseases. Here, we reviewed the regulatory role of lncRNA m6A methylation in a variety of diseases, and made a prospect of its application in stomatology.

[1]
Geula S,,Moshitch-Moshkovitz S,,Dominissini D,et al. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation[J]. Science2015347(6225):1002-1006. DOI:10.1126/science.1261417.
[2]
Zhao W,,Qi X,,Liu L,et al. Epigenetic regulation of m6A modifications in human cancer[J]. Mol Ther Nucleic Acids202019:405-412. DOI:10.1016/j.omtn.2019.11.022.
[3]
Zheng G,,Dahl JA,,Niu Y,et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility [J]. Mol Cell201349(1):18-29. DOI:10.1016/j.molcel.2012.10.015.
[4]
Wei J,,Liu F,,Lu Z,et al. Differential m6A,m6Am,and m1A demethylation mediated by FTO in the cell nucleus and cytoplasm[J]. Mol Cell201871(6):973-985,e1-e5. DOI:10.1016/j.molcel.2018.08.011.
[5]
Liao CH,,Wang YH,,Chang WW,et al. Leucine-rich repeat neuronal protein 1 regulates differentiation of embryonic stem cells by post-translational modifications of pluripotency factors [J]. Stem Cells201836(10):1514-1524. DOI:10.1002/stem.2862.
[6]
Batista PJ,,Molinie B,,Wang J,et al. m6A RNA modification controls cell fate transition in mammalian embryonic stem cells [J]. Cell Stem Cell201415(6):707-719. DOI:10.1016/j.stem.2014.09.019.
[7]
Chen T,,Hao YJ,,Zhang Y,et al. m6A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency[J]. Cell Stem Cell201516(3):289-301. DOI:10.1016/j.stem.2015.01.016.
[8]
Vu LP,,Cheng Y,,Kharas MG. The biology of m6A RNA methylation in normal and malignant hematopoiesis[J]. Cancer Discov20199(1):25-33. DOI:10.1158/2159-8290.CD-18-0959.
[9]
Wang Y,,Li Y,,Yue M,et al. N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications[J]. Nat Neurosci201821(2):195-206. DOI:10.1038/s41593-017-0057-1.
[10]
Chen M,,Wei L,,Law CT,et al. RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2[J]. Hepatology201867(6):2254-2270. DOI:10.1002/hep.29683.
[11]
Barbieri I,,Tzelepis K,,Pandolfini L,et al. Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control[J]. Nature2017552(7683):126-131. DOI:10.1038/nature24678.
[12]
Huang Y,,Su R,,Sheng Y,et al. Small-molecule targeting of oncogenic FTO demethylase in acute myeloid leukemia[J]. Cancer Cell201935(4):677-691,e1-e10. DOI:10.1016/j.ccell.2019.03.006.
[13]
Bansal H,,Yihua Q,,Iyer SP,et al. WTAP is a novel oncogenic protein in acute myeloid leukemia[J]. Leukemia201428(5):1171-1174. DOI:10.1038/leu.2014.16.
[14]
Yao Y,,Bi Z,,Wu R,et al. METTL3 inhibits BMSC adipogenic differentiation by targeting the JAK1/STAT5/C/EBPβ pathway via an m6A-YTHDF2-dependent manner[J]. FASEB J201933(6):7529-7544. DOI:10.1096/fj.201802644R.
[15]
Tian C,,Huang Y,,Li Q,et al. Mettl3 regulates osteogenic differentiation and alternative splicing of vegfa in bone marrow mesenchymal stem cells[J]. Int J Mol Sci201920(3):551. DOI:10.3390/ijms20030551.
[16]
Miao W,,Chen J,,Jia L,et al. The m6A methyltransferase METTL3 promotes osteosarcoma progression by regulating the m6A level of LEF1[J]. Biochem Biophys Res Commun2019516(3):719-725. DOI:10.1016/j.bbrc.2019.06.128.
[17]
Wang Z,,Li X. The role of noncoding RNA in hepatocellular carcinoma[J]. Gland Surg20132(1):25-29. DOI:10.3978/j.issn.2227-684X.2013.02.07.
[18]
Guttman M,,Rinn JL. Modular regulatory principles of large non-coding RNAs[J]. Nature2012482(7385):339-346. DOI:10.1038/nature10887.
[19]
Gutschner T,,Diederichs S. The hallmarks of cancer:A long non-coding RNA point of view[J]. RNA Biol20129(6):703-719. DOI:10.4161/rna.20481.
[20]
Pontier DB,,Gribnau J. Xist regulation and function explored [J]. Hum Genet2011130(2):223-236. DOI:10.1007/s00439-011-1008-7.
[21]
Kornienko AE,,Guenzl PM,,Barlow DP,et al. Gene regulation by the act of long non-coding RNA transcription[J]. BMC Biol201311:59. DOI:10.1186/1741-7007-11-59.
[22]
Rinn JL,,Kertesz M,,Wang JK,et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs[J]. Cell2007129(7):1311-1323. DOI:10.1016/j.cell.2007.05.022.
[23]
Mondal T,,Subhash S,,Vaid R,et al. MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures[J]. Nat Commun20156:7743. DOI:10.1038/ncomms8743.
[24]
O′Leary VB,,Ovsepian SV,,Carrascosa LG,et al. PARTICLE,a triplex-forming long ncRNA,regulates locus-specific methylation in response to low-dose irradiation[J]. Cell Rep201511(3):474-485. DOI:10.1016/j.celrep.2015.03.043.
[25]
Yakovchuk P,,Goodrich JA,,Kugel JF. B2 RNA and Alu RNA repress transcription by disrupting contacts between RNA polymerase Ⅱ and promoter DNA within assembled complexes [J]. Proc Natl Acad Sci U S A2009106(14):5569-5574. DOI:10.1073/pnas.0810738106.
[26]
Peterlin BM,,Brogie JE,,Price DH. 7SK snRNA:a noncoding RNA that plays a major role in regulating eukaryotic transcription [J]. Wiley Interdiscip Rev RNA20123(1):92-103. DOI:10.1002/wrna.106.
[27]
Feng J,,Bi C,,Clark BS,et al. The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator[J]. Genes Dev200620(11):1470-1484. DOI:10.1101/gad.1416106.
[28]
Sharma S,,Findlay GM,,Bandukwala HS,et al. Dephosphorylation of the nuclear factor of activated T cells(NFAT)transcription factor is regulated by an RNA-protein scaffold complex[J]. Proc Natl Acad Sci U S A2011108(28):11381-11386. DOI:10.1073/pnas.1019711108.
[29]
Beltran M,,Puig I,,Peña C,et al. A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition[J]. Genes Dev200822(6):756-769. DOI:10.1101/gad.455708.
[30]
Annilo T,,Kepp K,,Laan M. Natural antisense transcript of natriuretic peptide precursor A(NPPA):structural organization and modulation of NPPA expression[J]. BMC Mol Biol200910:81. DOI:10.1186/1471-2199-10-81.
[31]
Desrosiers R,,Friderici K,,Rottman F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells[J]. Proc Natl Acad Sci U S A197471(10):3971-3975. DOI:10.1073/pnas.71.10.3971.
[32]
Ma S,,Chen C,,Ji X,et al. The interplay between m6A RNA methylation and noncoding RNA in cancer[J]. J Hematol Oncol201912(1):121. DOI:10.1186/s13045-019-0805-7.
[33]
Patil DP,,Chen CK,,Pickering BF,et al. m6A RNA methylation promotes XIST-mediated transcriptional repression[J]. Nature2016537(7620):369-373. DOI:10.1038/nature19342.
[34]
Yang D,,Qiao J,,Wang G,et al. N6-methyladenosine modification of lincRNA 1281 is critically required for mESC differentiation potential[J]. Nucleic Acids Res201846(8):3906-3920. DOI:10.1093/nar/gky130.
[35]
Shang W,,Gao Y,,Tang Z,et al. The pseudogene Olfr29-ps1 promotes the suppressive function and differentiation of monocytic MDSCs[J]. Cancer Immunol Res20197(5):813-827. DOI:10.1158/2326-6066.CIR-18-0443.
[36]
Zhang X,,Hamblin MH,,Yin KJ. The long noncoding RNA Malat1:Its physiological and pathophysiological functions[J]. RNA Biol201714(12):1705-1714. DOI:10.1080/15476286.2017.1358347.
[37]
Kim J,,Piao HL,,Kim BJ,et al. Long noncoding RNA MALAT1 suppresses breast cancer metastasis[J]. Nat Genet201850(12):1705-1715. DOI:10.1038/s41588-018-0252-3.
[38]
Zhou KI,,Parisien M,,Dai Q,et al. N6-methyladenosine modification in a long noncoding RNA hairpin predisposes its conformation to protein binding[J]. J Mol Biol2016428(5 Pt A):822-833. DOI:10.1016/j.jmb.2015.08.021.
[39]
Wu Y,,Yang X,,Chen Z,et al. m6A-induced lncRNA RP11 triggers the dissemination of colorectal cancer cells via upregulation of Zeb1[J]. Mol Cancer201918(1):87. DOI:10.1186/s12943-019-1014-2.
[40]
Arshi A,,Sharifi FS,,Khorramian Ghahfarokhi M,et al. Expression analysis of MALAT1,GAS5,SRA,and NEAT1 lncRNAs in breast cancer tissues from young women and women over 45 years of age[J]. Mol Ther Nucleic Acids201812:751-757. DOI:10.1016/j.omtn.2018.07.014.
[41]
Ni W,,Yao S,,Zhou Y,et al. Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m6A reader YTHDF3[J]. Mol Cancer201918(1):143. DOI:10.1186/s12943-019-1079-y.
[42]
Zheng ZQ,,Li ZX,,Zhou GQ,et al. Long noncoding RNA FAM225A promotes nasopharyngeal carcinoma tumorigenesis and metastasis by acting as ceRNA to sponge miR-590-3p/miR-1275 and upregulate ITGB3[J]. Cancer Res201979(18):4612-4626. DOI:10.1158/0008-5472.CAN-19-0799.
[43]
Zhang S,,Zhao BS,,Zhou A,et al. m6A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program[J]. Cancer Cell201731(4):591-606,e1-e6. DOI:10.1016/j.ccell.2017.02.013.
[44]
Song Y,,Pan Y,,Wu M,et al. METTL3-Mediated lncRNA m6A modification in the osteogenic differentiation of human adipose-derived stem cells induced by NEL-Like 1 protein[J]. Stem Cell Rev Rep202117(6):2276-2290. DOI:10.1007/s12015-021-10245-4.
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