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摘要: 5-甲基胞嘧啶(5-methylcytosine,m5C)是RNA中重要的甲基化修饰之一,也是近年来的研究热点。随着甲基化测序技术的发展,在编码RNA及非编码RNA中均证实存在大量的m5C甲基化修饰。RNA m5C甲基化修饰受m5C甲基转移酶、去甲基化酶及m5C甲基化结合蛋白的调控。m5C甲基化修饰调节RNA的稳定性、转运、翻译和压力应激等,并参与调节肿瘤的发生发展、侵袭转移、肿瘤耐药等进程。本文对RNA m5C甲基化修饰的调控机制、功能以及在肿瘤中的研究进展进行综述,以期为肿瘤诊治研究提供新思路。Abstract: 5-methylcytosine (m5C) is an important post-translationally modified base in RNA formed by cytosine methylation. As the development of methylation sequencing techniques, extensive m5C modifications have been found in both coding and non-coding RNA. Incorporation of m5C into RNA is regulated by methyltransferases, demethylases, and m5C-binding proteins. m5C incorporation regulates RNA stability, transport, translation, and pressure stress. Recent studies have revealed that m5C incorporation into RNA is involved in the regulation of tumor pathogenesis, development, invasion, metastasis, and resistance. This article reviews m5C-mediated regulatory mechanisms and functions, and research progress on m5C-modified RNA functions in tumors, thus providing novel insights for developing innovative tumor diagnostic and therapeutic strategies.
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Key words:
- 5-methylcytosine (m5C) /
- encoding RNA /
- non-coding RNA /
- tumor
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[1] He Y, Zhang Q, Zheng Q, et al. Distinct 5-methylcytosine profiles of circular RNA in human hepatocellular carcinoma[J]. Am J Transl Res, 2020, 12(9):5719-5729. [2] He Y, Shi Q, Zhang Y, et al. Transcriptome-wide 5-methylcytosine functional profiling of long non-coding RNA in hepatocellular carcinoma[J]. Cancer Manage Res, 2020, 12:6877-6885. [3] Chen X, Li A, Sun BF, et al. 5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs[J]. Nat Cell Biol, 2019, 21(8):978-990. [4] Zhang Q, Zheng Q, Yu X, et al. Overview of distinct 5-methylcytosine profiles of messenger RNA in human hepatocellular carcinoma and paired adjacent non-tumor tissues[J]. J Transl Med, 2020, 18(1):245. [5] Xue M, Shi Q, Zheng L, et al. Gene signatures of m5C regulators may predict prognoses of patients with head and neck squamous cell carcinoma[J]. Am J Transl Res, 2020, 12(10):6841-6852. [6] Wang P, Wu M, Tu Z, et al. Identification of RNA: 5-methylcytosine methyltransferases-related signature for predicting prognosis in glioma[J]. Front Oncol, 2020, 10:1119. [7] Gao Y, Wang Z, Zhu Y, et al. NOP2/Sun RNA methyltransferase 2 promotes tumor progression via its interacting partner RPL6 in gallbladder carcinoma[J]. Cancer Sci, 2019, 110(11):3510-3519. [8] Sun Z, Xue S, Zhang M, et al. Aberrant NSUN2-mediated m5C modification of H19 lncRNA is associated with poor differentiation of hepatocellular carcinoma[J]. Oncogene, 2020, 39(45):6906-6919. [9] Jiang Z, Li S, Han MJ, et al. High expression of NSUN5 promotes cell proliferation via cell cycle regulation in colorectal cancer[J]. Am J Transl Res, 2020, 12(7):3858-3870. [10] Selmi T, Hussain S, Dietmann S, et al. Sequence- and structure-specific cytosine-5 mRNA methylation by NSUN6[J]. Nucl Acids Res, 2021, 49(2):1006-1022. [11] Xue C, Zhao Y, Li L. Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer[J]. Biomarker Res, 2020, 8:43. [12] Peng Z, Wang J, Shan B, et al. The long noncoding RNA LINC00312 induces lung adenocarcinoma migration and vasculogenic mimicry through directly binding YBX1[J]. Mole Cancer, 2018, 17(1):167. [13] Huang T, Chen W, Liu J, et al. Genome-wide identification of mRNA 5-methylcytosine in mammals[J]. Nat Struct Mol Biol, 2019, 26(5):380-388. [14] Li Q, Li X, Tang H, et al. NSUN2-mediated m5C methylation and METTL3/METTL14-Mediated m6A methylation cooperatively enhance p21 translation[J]. J Cell Biochem, 2017, 118(9):2587-2598. [15] Schumann U, Zhang HN, Sibbritt T, et al. Multiple links between 5-methylcytosine content of mRNA and translation[J]. BMC Biol, 2020, 18(1):40. [16] Yang X, Yang Y, Sun BF, et al. 5-methylcytosine promotes mRNA export-NSUN2 as the methyltransferase and ALYREF as an m(5)C reader[J]. Cell Res, 2017, 27(5):606-625. [17] Yang L, Perrera V, Saplaoura E, et al. m(5)C methylation guides systemic transport of messenger RNA over graft junctions in plants[J]. Curr Biol, 2019, 29(15):2465-2476. [18] Dev RR, Ganji R, Singh SP, et al. Cytosine methylation by DNMT2 facilitates stability and survival of HIV-1 RNA in the host cell during infection[J]. Biochem J, 2017, 474(12):2009-2026. [19] Kong W, Biswas A, Zhou D, et al. Nucleolar protein NOP2/NSUN1 suppresses HIV-1 transcription and promotes viral latency by competing with Tat for TAR binding and methylation[J]. PLoS Pathog, 2020, 16(3):e1008430. [20] He Y, Yu X, Li J, et al. Role of m(5)C-related regulatory genes in the diagnosis and prognosis of hepatocellular carcinoma[J]. Am J Transl Res, 2020, 12(3):912-922. [21] Mei L, Shen C, Miao R, et al. RNA methyltransferase NSUN2 promotes gastric cancer cell proliferation by repressing p57 by an mC-dependent manner[J]. Cell Death Dis, 2020, 11(4):270. [22] Xiang S, Ma Y, Shen J, et al. m5C RNA methylation primarily affects the ErbB and PI3K-Akt signaling pathways in gastrointestinal cancer[J]. Front Mol Biosci, 2020, (7):599340. [23] Cheng JX, Chen L, Li Y, et al. RNA cytosine methylation and methyltransferases mediate chromatin organization and 5-azacytidine response and resistance in leukaemia[J]. Nat Commun, 2018, 9(1):1163. [24] Cheray M, Etcheverry A, Jacques C, et al. Cytosine methylation of mature microRNAs inhibits their functions and is associated with poor prognosis in glioblastoma multiforme[J]. Mol Cancer, 2020, 19(1):36. [25] Chen H, Ge XL, Zhang ZY, et al. M(5)C regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in lung adenocarcinoma[J]. Transl Lung Cancer Res, 2021, 10(5):2172-2192. [26] Pan J, Huang Z, Xu Y. m5C-related lncRNAs predict overall survival of patients and regulate the tumor immune microenvironment in lung adenocarcinoma[J]. Front Cell and Dev Biol, 2021, 9:671821. [27] Pan J, Huang Z, Xu Y. m5C RNA methylation regulators predict prognosis and regulate the immune microenvironment in lung squamous cell carcinoma[J]. Front Oncol, 2021, 11:657466.
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