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原发性干燥综合征患者唾液腺组织ceRNA调控网络的构建

吴玲玲 凌华云 周颖 邱丽娟 王红 薛昱 陈慧娟 王廷睿 王斌

吴玲玲, 凌华云, 周颖, 邱丽娟, 王红, 薛昱, 陈慧娟, 王廷睿, 王斌. 原发性干燥综合征患者唾液腺组织ceRNA调控网络的构建[J]. 中华疾病控制杂志, 2022, 26(7): 777-783. doi: 10.16462/j.cnki.zhjbkz.2022.07.006
引用本文: 吴玲玲, 凌华云, 周颖, 邱丽娟, 王红, 薛昱, 陈慧娟, 王廷睿, 王斌. 原发性干燥综合征患者唾液腺组织ceRNA调控网络的构建[J]. 中华疾病控制杂志, 2022, 26(7): 777-783. doi: 10.16462/j.cnki.zhjbkz.2022.07.006
WU Ling-ling, LING Hua-yun, ZHOU Ying, QIU Li-juan, WANG Hong, XUE Yu, CHEN Hui-juan, WANG Ting-rui, WANG Bin. Construction and analysis of ceRNA network in salivary gland tissues of patients with primary Sjogren's syndrome[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2022, 26(7): 777-783. doi: 10.16462/j.cnki.zhjbkz.2022.07.006
Citation: WU Ling-ling, LING Hua-yun, ZHOU Ying, QIU Li-juan, WANG Hong, XUE Yu, CHEN Hui-juan, WANG Ting-rui, WANG Bin. Construction and analysis of ceRNA network in salivary gland tissues of patients with primary Sjogren's syndrome[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2022, 26(7): 777-783. doi: 10.16462/j.cnki.zhjbkz.2022.07.006

原发性干燥综合征患者唾液腺组织ceRNA调控网络的构建

doi: 10.16462/j.cnki.zhjbkz.2022.07.006
基金项目: 

国家自然科学基金 81573217

详细信息
    通讯作者:

    王斌,E-mail: wangbin@ahmu.edu.cn

  • 中图分类号: R593.2;R181

Construction and analysis of ceRNA network in salivary gland tissues of patients with primary Sjogren's syndrome

Funds: 

National Natural Science Foundation of China 81573217

More Information
  • 摘要:   目的  通过生物信息学方法构建原发性干燥综合征(primary Sjögren’s syndrome, pSS)患者唾液腺组织中的竞争内源性RNA(competing endogenous RNA, ceRNA)调控网络并探讨其发病机制。  方法  利用基因表达综合数据库(Gene Expression Omnibus, GEO)对pSS患者唾液腺组织中的信使RNA(messenger RNA, mRNA)、长链非编码RNA(long non-coding RNA, lncRNA)表达谱作差异分析。通过miRcode数据库和3个miRNA数据库(TargetScan、miRDB和miRWalk)获取与pSS有关的靶微小RNA(microRNA, miRNA)和靶mRNA,构建lncRNA-miRNA-mRNA的ceRNA调控网络,对ceRNA网络中差异表达基因(differentially expressed mRNAs, DEmRNAs)进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)通路富集分析。  结果  在ceRNA网络中有214个DEmRNAs。KEGG分析显示DEmRNAs的主要富集信号通路为丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)信号通路和腺苷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)信号通路,DEmRNAs中10个枢纽(Hub)基因分别为JUNCCND1、NRASDDX5、KAT2BVEGFASIRT1、CLTAMCM7和RPS6KA1。  结论  本研究通过构建ceRNA调控网络,发现网络中DEmRNAs主要富集MAPK和AMPK信号通路, 为进一步深入探讨原发性干燥综合征的诊断和治疗提供了新的思路。
  • 图  1  mRNA和lncRNA差异表达分析结果

    注:A表示DEmRNAs火山图;B表示DElncRNAs火山图;C表示DEmRNAs热图;D表示DElncRNAs热图。

    Figure  1.  Differential expression analysis of mRNA and lncRNA

    图  2  pSS的ceRNA调控网络

    Figure  2.  The ceRNA regulation network of pSS

    图  3  KEGG通路富集分析

    注:A和C表示上调DEmRNAs;B和D表示下调DEmRNAs。

    Figure  3.  KEGG pathway enrichment analysis

    图  4  ceRNA调控网络中的枢纽基因

    Figure  4.  Hub genes in ceRNA regulation network

    图  5  PPI互作网络图

    Figure  5.  Protein-protein interaction networks

    表  1  GEO数据集基本信息

    Table  1.   The basic information of GEO datasets

    GSE编号 平台 病例(n) 对照(n) 样本类型 数据类型 疾病
    GSE23117 GPL570 11 4 唾液腺组织 mRNA pSS
    GSE76013 GPL21242 4 4 唾液腺组织 lncRNA pSS
    下载: 导出CSV

    表  2  pSS相关lncRNA的靶miRNA

    Table  2.   Target mirnas of pSS related lncrnas

    编号 lncRNA miRNA
    1 C1orf112 hsa-miR-503
    2 CEACAM21 hsa-miR-138
    3 TFAP2B hsa-miR-132
    4 CELSR3 hsa-miR-503
    5 TRAF3IP3 hsa-miR-132
    6 TNFRSF9 hsa-miR-132
    7 ANKRD44 hsa-miR-130ac
    8 RASGRP2 hsa-miR-503
    9 RPS6KA6 hsa-miR-130ac
    10 LINC00426 hsa-miR-130ac
    注:表中只列出符合条件的前10位lncRNA和miRNA。
    下载: 导出CSV

    表  3  pSS相关miRNA的靶mRNA

    Table  3.   Target mirnas of pSS related lncrnas

    编号 miRNA mRNA miRDB miRTarBase TargetScan
    1 hsa-miR-1297 DEPDC1 1 1 1
    2 hsa-miR-142-3p PSMB5 1 1 1
    3 hsa-miR-23b-3p GJA1 1 1 1
    4 hsa-miR-17-5p SMOC1 1 1 1
    5 hsa-miR-107 POLD3 1 1 1
    6 hsa-miR-761 ZNF641 1 1 1
    7 hsa-miR-20b-5p ZNF532 1 1 1
    8 hsa-miR-17-5p MORF4L1 1 1 1
    9 hsa-miR-20b-5p FAM46C 1 1 1
    10 hsa-miR-137 PTGS2 1 1 1
    注:表中只列出符合条件的前10位lncRNA和miRNA; 1表示基因在对应数据库中存在。
    下载: 导出CSV
  • [1] Fox RI. Sjögren's syndrome[J]. Lancet, 2005, 366(9482): 321-331. DOI: 10.1016/s0140-6736(05)66990-5.
    [2] Mavragani CP. Mechanisms and new strategies for primary Sjögren's syndrome[J]. Annu Rev Med, 2017, 68: 331-343. DOI: 10.1146/annurev-med-043015-123313.
    [3] Patel R, Shahane A. The epidemiology of Sjögren's syndrome[J]. Clin Epidemiol, 2014, 6: 247-255. DOI: 10.2147/CLEP.S47399.
    [4] García-Carrasco M, Fuentes-Alexandro S, Escárcega RO, et al. Pathophysiology of Sjögren's syndrome[J]. Arch Med Res, 2006, 37(8): 921-932. DOI: 10.1016/j.arcmed.2006.08.002.
    [5] Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA translation and stability by microRNAs[J]. Annu RevBiochem, 2010, 79: 351-379. DOI: 10.1146/annurev-biochem-060308-103103.
    [6] Salmena L, Poliseno L, Tay Y, et al. A ceRNA hypothesis: the Rosetta stone of a hidden RNA language?[J]. Cell, 2011, 146(3): 353-358. DOI: 10.1016/j.cell.2011.07.014.
    [7] Fitzgerald KA, Caffrey DR. Long noncoding RNAs in innate and adaptive immunity[J]. Curr Opin Immunol, 2014, 26: 140-146. DOI: 10.1016/j.coi.2013.12.001.
    [8] Li M, Guan H. Noncoding RNAs regulating NF-κB signaling[J]. Adv Exp Med Biol, 2016, 927: 317-336. DOI: 10.1007/978-981-10-1498-7_12.
    [9] Marques-Rocha JL, Samblas M, Milagro FI, et al. Noncoding RNAs, cytokines, and inflammation-related diseases[J]. Faseb J, 2015, 29(9): 3595-3611. DOI: 10.1096/fj.14-260323.
    [10] Dolcino M, Tinazzi E, Vitali C, et al. Long non-coding RNAs modulate Sjögren's syndrome associated gene expression and are involved in the pathogenesis of the disease[J]. J Clin Med, 2019, 8(9): 1349. DOI: 10.3390/jcm8091349.
    [11] Cheng C, Zhou J, Chen R, et al. Predicted disease-specific immune infiltration patterns decode the potential mechanisms of long non-coding RNAs in primary Sjogren's syndrome[J]. Front Immunol, 2021, 12: 624614. DOI: 10.3389/fimmu.2021.624614.
    [12] Iborra S, Soto M, Stark-Aroeira L, et al. H-ras and N-ras are dispensable for T-cell development and activation but critical for protective Th1 immunity[J]. Blood, 2011, 117(19): 5102-5111. DOI: 10.1182/blood-2010-10-315770.
    [13] Koutelou E, Farria AT, Dent SYR. Complex functions of Gcn5 and Pcaf in development and disease[J]. Biochim Biophys Acta Gene Regul Mech, 2021, 1864(2): 194609. DOI: 10.1016/j.bbagrm.2020.194609.
    [14] Liu Y, Bao C, Wang L, et al. Complementary roles of GCN5 and PCAF in Foxp3+ T-Regulatory cells[J]. Cancers (Basel), 2019, 11(4): 554. DOI: 10.3390/cancers11040554.
    [15] Kim SR, Lee KS, Park SJ, et al. Involvement of sirtuin 1 in airway inflammation and hyperresponsiveness of allergic airway disease[J]. J Allergy Clin Immunol, 2010, 125(2): 449-460. DOI: 10.1016/j.jaci.2009.08.009.
    [16] Wang J, Zhao C, Kong P, et al. Treatment with NAD(+) inhibited experimental autoimmune encephalomyelitis by activating AMPK/SIRT1 signaling pathway and modulating Th1/Th17 immune responses in mice[J]. Int Immunopharmacol, 2016, 39: 287-294. DOI: 10.1016/j.intimp.2016.07.036.
    [17] Yang H, Bi Y, Xue L, et al. Multifaceted modulation of SIRT1 in cancer and inflammation[J]. Crit Rev Oncog, 2015, 20(1-2): 49-64. DOI: 10.1615/critrevoncog.2014012374.
    [18] Zeng H, Chi H. Metabolic control of regulatory T cell development and function[J]. Trends Immunol, 2015, 36(1): 3-12. DOI: 10.1016/j.it.2014.08.003.
    [19] Singh N, Cohen PL. The T cell in Sjogren's syndrome: force majeure, not spectateur[J]. J Autoimmun, 2012, 39(3): 229-233. DOI: 10.1016/j.jaut.2012.05.019.
    [20] Maehara T, Moriyama M, Hayashida JN, et al. Selective localization of T helper subsets in labial salivary glands from primary Sjögren's syndrome patients[J]. Clin Exp Immunol, 2012, 169(2): 89-99. DOI: 10.1111/j.1365-2249.2012.04606.x.
    [21] Gougopoulou DM, Kiaris H, Ergazaki M, et al. Mutations and expression of the ras family genes in leukemias[J]. Stem Cells, 1996, 14(6): 725-729. DOI: 10.1002/stem.140725.
    [22] Downey M. Non-histone protein acetylation by the evolutionarily conserved GCN5 and PCAF acetyltransferases[J]. Biochim Biophys Acta Gene Regul Mech, 2021, 1864(2): 194608. DOI: 10.1016/j.bbagrm.2020.194608.
    [23] Carvalho JF, Blank M, Shoenfeld Y. Vascular endothelial growth factor (VEGF) in autoimmune diseases[J]. J Clin Immunol, 2007, 27(3): 246-256. DOI: 10.1007/s10875-007-9083-1.
    [24] Roy R, Zhang B, Moses MA. Making the cut: protease-mediated regulation of angiogenesis[J]. Exp Cell Res, 2006, 312(5): 608-622. DOI: 10.1016/j.yexcr.2005.11.022.
    [25] Sisto M, Lisi S, Lofrumento DD, et al. Sjögren's syndrome pathological neovascularization is regulated by VEGF-A-stimulated TACE-dependent crosstalk between VEGFR2 and NF-κB[J]. Genes Immun, 2012, 13(5): 411-420. DOI: 10.1038/gene.2012.9.
    [26] Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases[J]. Microbiol Mol Biol Rev, 2011, 75(1): 50-83. DOI: 10.1128/mmbr.00031-10.
    [27] Culbert AA, Skaper SD, Howlett DR, et al. MAPK-activated protein kinase 2 deficiency in microglia inhibits pro-inflammatory mediator release and resultant neurotoxicity. Relevance to neuroinflammation in a transgenic mouse model of Alzheimer disease[J]. J Biol Chem, 2006, 281(33): 23658-23667. DOI: 10.1074/jbc.m513646200.
    [28] Gurgis FM, Ziaziaris W, Munoz L. Mitogen-activated protein kinase-activated protein kinase 2 in neuroinflammation, heat shock protein 27 phosphorylation, and cell cycle: role and targeting[J]. Mol Pharmacol, 2014, 85(2): 345-356. DOI: 10.1124/mol.113.090365.
    [29] Krementsov DN, Thornton TM, Teuscher C, et al. The emerging role of p38 mitogen-activated protein kinase in multiple sclerosis and its moDElncRNAs[J]. Mol Cell Biol, 2013, 33(19): 3728-3734. DOI: 10.1128/mcb.00688-13.
    [30] Fu J, Shi H, Cao N, et al. Toll-like receptor 9 signaling promotes autophagy and apoptosis via divergent functions of the p38/JNK pathway in human salivary gland cells[J]. Exp Cell Res, 2019, 375(2): 51-59. DOI: 10.1016/j.yexcr.2018.12.027.
    [31] Boyer PD, Chance B, Ernster L, et al. Oxidative phosphorylation and photophosphorylation[J]. Annu Rev Biochem, 1977, 46: 955-966. DOI: 10.1146/annurev.bi.46.070177.004515.
    [32] Katsiougiannis S, Tenta R, Skopouli FN. Activation of AMP-activated protein kinase by adiponectin rescues salivary gland epithelial cells from spontaneous and interferon-gamma-induced apoptosis[J]. A hritis Rheum, 2010, 62(2): 414-419. DOI: 10.1002/art.27239.
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出版历程
  • 收稿日期:  2021-10-31
  • 修回日期:  2022-02-15
  • 网络出版日期:  2022-07-19
  • 刊出日期:  2022-07-10

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