mRNA m6A修饰与口腔疾病

摘要/Abstract

摘要： N6-甲基腺苷（m6A）甲基化作为真核生物 mRNA 中最丰富的表观遗传修饰，广泛参与进干细胞分化进程调控、哺乳动物发育、肿瘤产生和免疫调控等多种生命过程中。m6A甲基化过程是可逆性修饰，由甲基转移酶、去甲基化酶和甲基化阅读蛋白组成。近年来，多篇文章表明m6A修饰在口腔组织发育和疾病中起到了重要作用。本文综述m6A在口腔疾病的研究进展，重点讨论在牙、颌骨、关节、黏膜等组织的调控作用及机制。

关键词: mRNA甲基化, m6A修饰, 口腔疾病

Abstract: N6-methyladenosine (m6A) is the most prevalent epigenetic modification in eukaryotic mRNAs and involves in multiple biological processes. As a reversible modification, the process m6A counts on three types of proteins: Writers, Erasers and Readers. Recently, emerging evidence elucidates the role of m6A modification in the development of oral tissues and progression of oral diseases. This review summarized the recent papers reporting the research progress of m6A in oral diseases, mainly discussing its regulation of tooth and mandible development, as well as temporomandibular arthritis and mucosal disorders.

Key words: mRNA甲基化, m6A修饰, 口腔疾病

宋薇盛睿袁泉. mRNA m6A修饰与口腔疾病[J]. 口腔生物医学, 2023, 14(1): 1-5.

参考文献 46

[1]	Zhao B S, Roundtree I A, He C.Post-transcriptional gene regulation by mRNA modifications[J].Nature reviews Molecular cell biology, 2017, 18(1):31-42
[2]	Morscher R J, Ducker G S, Li S H-J, et al.Mitochondrial translation requires folate-dependent tRNA methylation[J].Nature, 2018, 554(7690):128-132
[3]	Sergiev P V, Aleksashin N A, Chugunova A A, et al.Structural and evolutionary insights into ribosomal RNA methylation[J].Nature chemical biology, 2018, 14(3):226-235
[4]	Li G, Ma L, He S, et al.WTAP-mediated m6A modification of lncRNA NORAD promotes intervertebral disc degeneration[J].Nature communications, 2022, 13(1):1-15
[5]	Desrosiers R, Friderici K, Rottman F.Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells[J].Proceedings of the National Academy of Sciences, 1974, 71(10):3971-3975
[6]	Fu Y, Dominissini D, Rechavi G, et al.Gene expression regulation mediated through reversible m6A RNA methylation[J].Nature Reviews Genetics, 2014, 15(5):293-306
[7]	Shi H, Wei J, He C.Where,when,and how: context-dependent functions of RNA methylation writers,readers,and erasers[J].Molecular cell, 2019, 74(4):640-650
[8]	Roundtree I A, Evans M E, Pan T, et al.Dynamic RNA modifications in gene expression regulation[J].Cell, 2017, 169(7):1187-1200
[9]	Engel M, Eggert C, Kaplick P M, et al.The role of m6Am-RNA methylation in stress response regulation[J].Neuron, 2018, 99(2):389-403
[10]	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
[11]	Frye M, Harada B T, Behm M, et al.RNA modifications modulate gene expression during development[J].Science, 2018, 361(6409):1346-1349
[12]	Tian C, Chai J, Liu W, et al.Role of the Demethylase AlkB Homolog H5 in the Promotion of Dentinogenesis[J].Frontiers in physiology, 2022, 13:923185-
[13]	Sheng R, Wang Y, Wu Y, et al.METTL3‐Mediated m6A mRNA Methylation Modulates Tooth Root Formation by Affecting NFIC Translation[J].Journal of Bone and Mineral Research, 2021, 36(2):412-423
[14]	Cai W, Ji Y, Han L, et al.METTL3-dependent glycolysis regulates dental pulp stem cell differentiation[J].Journal of Dental Research, 2022, 101(5):580-589
[15]	Luo H, Liu W, Zhang Y, et al.METTL3-mediated m6A modification regulates cell cycle progression of dental pulp stem cells[J].Stem cell research & therapy, 2021, 12(1):1-13
[16]	Feng Z, Li Q, Meng R, et al.METTL 3 regulates alternative splicing of MyD88 upon the lipopolysaccharide‐induced inflammatory response in human dental pulp cells[J].Journal of cellular and molecular medicine, 2018, 22(5):2558-2568
[17]	Manlove A E, Romeo G, Venugopalan S R.Craniofacial growth: current theories and influence on management[J].Oral and Maxillofacial Surgery Clinics, 2020, 32(2):167-175
[18]	Percival C J, Richtsmeier J T.Angiogenesis and intramembranous osteogenesis[J].Developmental Dynamics, 2013, 242(8):909-922
[19]	Salhotra A, Shah H N, Levi B, et al.Mechanisms of bone development and repair[J].Nature reviews Molecular cell biology, 2020, 21(11):696-711
[20]	Hinton R, Jing Y, Jing J, et al.Roles of chondrocytes in endochondral bone formation and fracture repair[J].Journal of dental research, 2017, 96(1):23-30
[21]	Wu Y, Xie L, Wang M, et al.Mettl3-mediated m6A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis[J].Nature communications, 2018, 9(1):1-12
[22]	Richard E M, Polla D L, Assir M Z, et al.Bi-allelic variants in METTL5 cause autosomal-recessive intellectual disability and microcephaly[J].The American Journal of Human Genetics, 2019, 105(4):869-878
[23]	Lei K, Xu R, Wang Q, et al.METTL5 regulates cranial suture fusion via Wnt signaling[J].Fundamental Research, 2022.
[24]	Jiang W, Zhu P, Huang F, et al.The RNA Methyltransferase METTL3 Promotes Endothelial Progenitor Cell Angiogenesis in Mandibular Distraction Osteogenesis via the PI3K/AKT Pathway[J].Frontiers in Cell and Developmental Biology, 2021, 9.
[25]	Golden E J, Larson E D, Shechtman L A, et al.Onset of taste bud cell renewal starts at birth and coincides with a shift in SHH function[J].Elife, 2021, 10:64013-
[26]	Xiong Q, Liu C, Zheng X, et al.METTL3-mediated m6A RNA methylation regulates dorsal lingual epithelium homeostasis[J].International Journal of Oral Science, 2022, 14(1):1-10
[27]	Zhang X, Zhang S, Yan X, et al.m6A regulator‐mediated RNA methylation modification patterns are involved in immune microenvironment regulation of periodontitis[J].Journal of cellular and molecular medicine, 2021, 25(7):3634-3645
[28]	Mo X, Lei S, Zhang Y, et al.Genome-wide enrichment of m6A-associated single-nucleotide polymorphisms in the lipid loci[J].The Pharmacogenomics Journal, 2019, 19(4):347-357
[29]	Lin W, Xu H, Wu Y, et al.In silico genome‐wide identification of m6A‐associated SNPs as potential functional variants for periodontitis[J].Journal of Cellular Physiology, 2020, 235(2):900-908
[30]	Genco R J, Sanz M.Clinical and public health implications of periodontal and systemic diseases: An overview[J].Periodontology, 2020, 83(1):7-13
[31]	Hajishengallis G, Chavakis T.Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities[J].Nature Reviews Immunology, 2021, 21(7):426-440
[32]	Ding D, Liu G, Gao J, et al.Unveiling the m6A Methylation Regulator Links between Prostate Cancer and Periodontitis by Transcriptomic Analysis[J].Disease Markers, 2022, 2022.
[33]	Wang X, Zhang J, Gan Y, et al.Current understanding of pathogenesis and treatment of TMJ osteoarthritis[J].Journal of dental research, 2015, 94(5):666-673
[34]	He Y, Wang W, Xu X, et al.Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through mediating Bcl2 stability via Ythdf1-mediated m6A modification[J].Bone, 2022, 154:116182-
[35]	Wu Z, Lin W, Yuan Q, et al.A genome-wide association analysis: m6A-SNP related to the onset of oral ulcers[J].Frontiers in immunology, 2022, 13.
[36]	Shen Y-W, Shih Y-H, Fuh L-J, et al.Oral submucous fibrosis: a review on biomarkers,pathogenic mechanisms,and treatments[J].International Journal of Molecular Sciences, 2020, 21(19):7231-
[37]	Li X, Gao Y, Chen W, et al.N6‐methyladenosine modification contributes to arecoline‐mediated oral submucosal fibrosis[J].Journal of Oral Pathology & Medicine, 2022: e13292.
[38]	Yu J-S, Chen Y-T, Chiang W-F, et al.Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan[J].Proceedings of the National Academy of Sciences, 2016, 113(41):11549-11554
[39]	Song X, Yang X, Narayanan R, et al.Oral squamous cell carcinoma diagnosed from saliva metabolic profiling[J].Proceedings of the National Academy of Sciences, 2020, 117(28):16167-16173
[40]	Liu L, Wu Y, Li Q, et al.METTL3 promotes tumorigenesis and metastasis through BMI1 m6A methylation in oral squamous cell carcinoma[J].Molecular Therapy, 2020, 28(10):2177-2190
[41]	Zhao W, Cui Y, Liu L, et al.METTL3 facilitates oral squamous cell carcinoma tumorigenesis by enhancing c-Myc stability via YTHDF1-mediated m6A modification[J].Molecular Therapy-Nucleic Acids, 2020, 20:1-12
[42]	Wu S, Makeudom A, Sun X, et al.Overexpression of methyltransferase‐like 3 and 14 in oral squamous cell carcinoma[J].Journal of Oral Pathology & Medicine, 2022, 51(2):134-145
[43]	Xu L, Yu C, Du X-J.Prognostic Evaluation for Oral Squamous Cell Carcinoma: A Novel Method Based on m6A Methylation Regulators[J].Current Medical Science, 2022, 42(4):841-846
[44]	Ai Y, Liu S, Luo H, et al.METTL3 Intensifies the Progress of Oral Squamous Cell Carcinoma via Modulating the m6A Amount of PRMT5 and PD-L1[J].Journal of Immunology Research, 2021, 2021.
[45]	Wang F, Liao Y, Zhang M, et al.N6-methyladenosine demethyltransferase FTO-mediated autophagy in malignant development of oral squamous cell carcinoma[J].Oncogene, 2021, 40(22):3885-3898
[46]	Wang F, Zhu Y, Cai H, et al.N6-methyladenosine methyltransferase METTL14-mediated autophagy in malignant development of oral squamous cell carcinoma[J].Frontiers in oncology, 2021, 11.