鼻息肉基因启动子甲基化谱的研究

白伟良; 谭海燕; 周倩; 王枭维; 李进兴

doi:10.13201/j.issn.1001-1781.2018.08.010

鼻息肉基因启动子甲基化谱的研究

- 中国医科大学附属盛京医院耳鼻喉科(沈阳, 110004)
基金项目:
辽宁省科学事业公益研究基金 (No:2013001010)

沈阳市科学技术计划 (No:F11-264-1-07, F13-220-9-21)

详细信息

通讯作者: 白伟良, E-mail:bweiliangcmu@163.com

中图分类号: R765.25

收稿日期: 2018-01-07

The exploration of gene promoter methylation profiling in nasal polyp

- Department of Otorhinolaryngology, Shengjing Hospital, China Medical University, Shenyang, 110004, China

More Information

Corresponding author: BAI Weiliang, E-mail: bweiliangcmu@163.com

Received Date: 07 January 2018

摘要

摘要: 目的: 研究鼻息肉的基因启动子甲基化表达谱的情况,探寻其与正常鼻腔黏膜之间的启动子甲基化差异。方法: 提取鼻息肉及正常对照组鼻腔黏膜中的DNA,经过免疫沉淀及扩增后,将Cy3/5标记的DNA在NimbleGen公司HG18 CpG启动子甲基化基因芯片上进行杂交。应用Axon GenePix 4000B scanner进行扫描,应用NimbleScan软件进行图像分析,然后对筛选出的差异基因进行信号通路分析,并Real-time PCR验证。结果: 在鼻腔黏膜或鼻息肉组织中检测出存在CpG岛高甲基化状态的基因3 010个,其中正常鼻腔黏膜组织甲基化阴性,而鼻息肉组织有高甲基化状态的基因79个(2.62%);正常鼻腔黏膜组织基因甲基化阳性,而鼻息肉组织中甲基化阴性的基因有321个(10.66%)。正常鼻腔黏膜组织甲基化阴性,而鼻息肉组织均有高甲基化状态的基因有3个信号通路;正常鼻腔黏膜组织基因甲基化阳性,而鼻息肉组织中甲基化阴性的基因有14个信号通路。结论: 基因启动子甲基化在鼻息肉发生发展中起重要作用,鼻息肉启动子甲基化谱研究为探求鼻息肉发生机制提供了有益的线索。
- 鼻息肉 /
- 基因芯片 /
- 启动子 /
- 甲基化
Abstract: Objective: To explore the gene promoter methylation profiles of nasal polyp, and to analysis the promoter methylation differences between the nasal polyp and the normal nasal mucosa.Method: Total DNA of the nasal polyp tissues and normal nasal mucosa were extracted. After immunoprecipitation and whole genome amplification, the DNA was labeled with Cy3/5 and hybridized in NimbleGen hybridization chamber. For array hybridization, Roche Nimblegen's CpG Promoter array was used. The slides were scanned using the Axon GenePix 4000B microarray scanner. The different genes were analyzed through pathway and verified by Real-time PCR.Result: 3 010 genes were found to have promoter hypermethylation in normal nasal mucosa or nasal polyp. 2.62% (79/3 010) of the genes had promoter hypermethylation in all the nasal polyps, which were negative in normal nasal mucosa. 10.66% (321/3 010) of the genes had promoter hypermethylation in normal nasal mucosa, which were negative in all the nasal polyps. Three pathways were found in the promoter hypermethylation of the nasal polyps. Fourteen pathways were found in the negative hypermethylation of the nasal polyps.Conclusion: Genes promoter methylation plays an important role in the development of nasal polyps, and the gene promoter methylation profiling may yield new some clues on the mechanism of nasal polyps.
- nasal polyps /
- gene chip /
- promoter /
- methylation

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参考文献(14)

[1]	ZAHIRUDDIN A S, GRANT J A, SUR S.Role of epigenetics and DNA-damage in asthma[J].Curr Opin Allergy Clin Immunol, 2018, 18:32-37.
[2]	CHUANG T D, KHORRAM O.Glucocorticoids regulate MiR-29clevels in vascular smooth muscle cells through transcriptional and epigenetic mechanisms[J].Life Sci, 2017, 186:87-91.
[3]	ZHANG X, BIAGINI MYERS J M, YADAGIRI V K, et al.Nasal DNA methylation differentiates corticosteroid treatment response in pediatric asthma:A pilot study[J].PLoS One, 2017, 12:e0186150.
[4]	DENNIS S K, LAM K, LUONG A.A Review of Classification Schemes for Chronic Rhinosinusitis with Nasal Polyposis Endotypes[J].Laryngoscope Investig Otolaryngol, 2016, 1:130-134.
[5]	MATTOS J L, WOODARD C R, PAYNE S C.Trends in common rhinologic illnesses:analysis of U.S.healthcare surveys 1995-2007[J].Int Forum Allergy Rhinol, 2011, 1:3-12.
[6]	DEVRIES A, VERCELLI D.Epigenetics in allergic diseases[J].Curr Opin Pediatr, 2015, 27:719-723.
[7]	KIM J Y, KIM D K, YU M S, et al.Role of epigenetics in the pathogenesis of chronic rhinosinusitis with nasal polyps[J].Mol Med Rep, 2018, 17:1219-1227.
[8]	FREEMAN A F, OLIVIER K N.Hyper-IgE Syndromes and the Lung[J].Clin Chest Med, 2016, 37:557-567.
[9]	GREF A, MERID S K, GRUZIEVA O, et al.Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up[J].Am J Respir Crit Care Med, 2017, 195:1373-1383.
[10]	KOVACIC M B, MYERS J M, WANG N, et al.I-dentification of KIF3A as a novel candidate gene for childhood asthma using RNA expression and population allelic frequencies differences[J].PLoS One, 2011, 6:e23714.
[11]	HU M, OU-YANG H F, HAN X P, et al.KyoT2 downregulates airway remodeling in asthma[J].Int JClin Exp Pathol, 2015, 8:14171-14179.
[12]	LIU L Y, WANG H, XENAKIS J J, et al.Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils[J].Allergy, 2015, 70:805-812.
[13]	DUAN C, LI C W, ZHAO L, et al.Differential Expression Patterns of EGF, EGFR, and ERBB4 in Nasal Polyp Epithelium[J].PLoS One, 2016, 11:e0156949.
[14]	BOBIC S, HOX V, CALLEBAUT I, et al.Vascular endothelial growth factor receptor 1expression in nasal polyp tissue[J].Allergy, 2014, 69:237-245.