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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Novel DNA Promoter Hypermethylation in Nasal Epithelium of Asthma

Author(s): Zhimin Zeng, Yuxia Liang, Changyi Xu, Weiping Tan, Lijuan Du, Yangli Liu*, Fengjia Chen* and Yubiao Guo*

Volume 26, Issue 10, 2023

Published on: 27 December, 2022

Page: [1879 - 1887] Pages: 9

DOI: 10.2174/1386207326666221028123802

Price: $65

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Abstract

Background: Abnormal epigenetic alterations influenced by external factors and affecting DNA expression contribute to the development of asthma. However, the role of the nasal epithelium in airway inflammation remains unknown.

Objective: The objective of this study is to identify novel DNA promoter hypermethylation, which suppresses mRNA expression in nasal epithelial of asthma.

Methods: Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Gene expression and DNA promoter methylation sites in key correlated modules between asthma and normal were identified by weighted gene co-expression network analysis. Gene Oncology and Kyoto Encyclopedia of Genes and Genomes were conducted to analyse the function of genes. Further validation was performed in human BEAS-2B cells challenged by IL-4 or IL-13.

Results: Lightcyan, lightgreen, midnightblue, cyan and tan modules in the mRNA expression dataset showed a close relationship with asthma, in which genes were enriched in TNF, IL-17, ErbB, MAPK and Estrogen signalling pathways. Blue and turquoise modules in the methylation profiling dataset were associated with asthma. Forty nine lowly expressed genes were identified to be correlated with aberrant DNA hypermethylation of promoters. Among these genes, the mRNA levels of BCL10, GADD45B, LSR and SQSTM1 were downregulated in BEAS-2B cells challenged with IL-4 or IL-13.

Conclusion: Four potential genes in the nasal epithelium, by hypermethylating their own DNA promoter, might mediate the inflammatory response in the pathogenesis of asthma. Analyzing epigenomic data by integrated bioinformatics helps to understand the role of DNA methylation in asthma, with the goal of providing new perspectives for diagnosis and therapy.

Keywords: Asthma, nasal epithelium, transcriptome, methylome, WGCNA, hypermethylation.

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[1]
Patel, K.P.; Giraud, A.S.; Samuel, C.S.; Royce, S.G. Combining an epithelial repair factor and anti-fibrotic with a corticosteroid offers optimal treatment for allergic airways disease. Br. J. Pharmacol., 2016, 173(12), 2016-2029.
[http://dx.doi.org/10.1111/bph.13494] [PMID: 27060978]
[2]
Lin, J.T.; Wang, W.Q.; Zhou, X.; Wang, C.Z.; Huang, M.; Cai, S.X.; Chen, P.; Lin, Q.C.; Zhou, J.Y.; Gu, Y.H.; Yuan, Y.D.; Sun, D.J.; Yang, X.H.; Yang, L.; Huo, J.M.; Chen, Z.C.; Jiang, P.; Zhang, J.; Ye, X.W.; Liu, H.G.; Tang, H.P.; Liu, R.Y.; Liu, C.T.; Zhang, W.; Hu, C.P.; Chen, Y.Q.; Liu, X.J.; Dai, L.M.; Zhou, W.; Huang, Y.J.; Xu, J.Y. The level of asthma control in China from a national asthma control survey. Zhonghua Jie He He Hu Xi Za Zhi, 2017, 40(7), 494-498.
[PMID: 28728272]
[3]
Daya, M.; Rafaels, N.; Brunetti, T.M.; Chavan, S.; Levin, A.M.; Shetty, A.; Gignoux, C.R.; Boorgula, M.P.; Wojcik, G.; Campbell, M.; Vergara, C.; Torgerson, D.G.; Ortega, V.E.; Doumatey, A.; Johnston, H.R.; Acevedo, N.; Araujo, M.I.; Avila, P.C.; Belbin, G.; Bleecker, E.; Bustamante, C.; Caraballo, L.; Cruz, A.; Dunston, G.M.; Eng, C.; Faruque, M.U.; Ferguson, T.S.; Figueiredo, C.; Ford, J.G.; Gan, W.; Gourraud, P.A.; Hansel, N.N.; Hernandez, R.D.; Herrera-Paz, E.F.; Jiménez, S.; Kenny, E.E.; Knight-Madden, J.; Kumar, R.; Lange, L.A.; Lange, E.M.; Lizee, A.; Maul, P.; Maul, T.; Mayorga, A.; Meyers, D.; Nicolae, D.L.; O’Connor, T.D.; Oliveira, R.R.; Olopade, C.O.; Olopade, O.; Qin, Z.S.; Rotimi, C.; Vince, N.; Watson, H.; Wilks, R.J.; Wilson, J.G.; Salzberg, S.; Ober, C.; Burchard, E.G.; Williams, L.K.; Beaty, T.H.; Taub, M.A.; Ruczinski, I.; Mathias, R.A.; Barnes, K.C. Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations. Nat. Commun., 2019, 10(1), 880.
[http://dx.doi.org/10.1038/s41467-019-08469-7] [PMID: 30787307]
[4]
Alashkar Alhamwe, B.; Alhamdan, F.; Ruhl, A.; Potaczek, D.P.; Renz, H. The role of epigenetics in allergy and asthma development. Curr. Opin. Allergy Clin. Immunol., 2020, 20(1), 48-55.
[http://dx.doi.org/10.1097/ACI.0000000000000598] [PMID: 31633569]
[5]
Tumes, D.J.; Papadopoulos, M.; Endo, Y.; Onodera, A.; Hirahara, K.; Nakayama, T. Epigenetic regulation of T-helper cell differentiation, memory, and plasticity in allergic asthma. Immunol. Rev., 2017, 278(1), 8-19.
[http://dx.doi.org/10.1111/imr.12560] [PMID: 28658556]
[6]
Yang, I.V.; Richards, A.; Davidson, E.J.; Stevens, A.D.; Kolakowski, C.A.; Martin, R.J.; Schwartz, D.A. The nasal methylome: A key to understanding allergic asthma. Am. J. Respir. Crit. Care Med., 2017, 195(6), 829-831.
[http://dx.doi.org/10.1164/rccm.201608-1558LE] [PMID: 28294656]
[7]
Cardenas, A.; Sordillo, J.E.; Rifas-Shiman, S.L.; Chung, W.; Liang, L.; Coull, B.A.; Hivert, M.F.; Lai, P.S.; Forno, E.; Celedón, J.C.; Litonjua, A.A.; Brennan, K.J.; DeMeo, D.L.; Baccarelli, A.A.; Oken, E.; Gold, D.R. The nasal methylome as a biomarker of asthma and airway inflammation in children. Nat. Commun., 2019, 10(1), 3095.
[http://dx.doi.org/10.1038/s41467-019-11058-3] [PMID: 31300640]
[8]
Qi, C.; Jiang, Y.; Yang, I.V.; Forno, E.; Wang, T.; Vonk, J.M.; Gehring, U.; Smit, H.A.; Milanzi, E.B.; Carpaij, O.A.; Berg, M.; Hesse, L.; Brouwer, S.; Cardwell, J.; Vermeulen, C.J.; Acosta-Pérez, E.; Canino, G.; Boutaoui, N.; van den Berge, M.; Teichmann, S.A.; Nawijn, M.C.; Chen, W.; Celedón, J.C.; Xu, C.J.; Koppelman, G.H. Nasal DNA methylation profiling of asthma and rhinitis. J. Allergy Clin. Immunol., 2020, 145(6), 1655-1663.
[http://dx.doi.org/10.1016/j.jaci.2019.12.911] [PMID: 31953105]
[9]
Aryee, M.J.; Jaffe, A.E.; Corrada-Bravo, H.; Ladd-Acosta, C.; Feinberg, A.P.; Hansen, K.D.; Irizarry, R.A. Minfi: A flexible and comprehensive bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics, 2014, 30(10), 1363-1369.
[http://dx.doi.org/10.1093/bioinformatics/btu049] [PMID: 24478339]
[10]
Ritchie, M.E.; Phipson, B.; Wu, D.; Hu, Y.; Law, C.W.; Shi, W.; Smyth, G.K. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res., 2015, 43(7), e47.
[http://dx.doi.org/10.1093/nar/gkv007] [PMID: 25605792]
[11]
Irizarry, R.A.; Hobbs, B.; Collin, F.; Beazer-Barclay, Y.D.; Antonellis, K.J.; Scherf, U.; Speed, T.P. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics, 2003, 4(2), 249-264.
[http://dx.doi.org/10.1093/biostatistics/4.2.249] [PMID: 12925520]
[12]
Langfelder, P.; Horvath, S. WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics, 2008, 9(1), 559.
[http://dx.doi.org/10.1186/1471-2105-9-559] [PMID: 19114008]
[13]
Benincasa, G.; DeMeo, D.L.; Glass, K.; Silverman, E.K.; Napoli, C. Epigenetics and pulmonary diseases in the horizon of precision medicine: A review. Eur. Respir. J., 2021, 57(6), 2003406.
[http://dx.doi.org/10.1183/13993003.03406-2020] [PMID: 33214212]
[14]
Aslani, M.R.; Sharghi, A.; Boskabady, M.H.; Ghobadi, H.; Keyhanmanesh, R.; Alipour, M.R.; Ahmadi, M.; Saadat, S.; Naghizadeh, P. Altered gene expression levels of IL-17/TRAF6/MAPK/USP25 axis and pro-inflammatory cytokine levels in lung tissue of obese ovalbumin-sensitized rats. Life Sci., 2022, 296, 120425.
[http://dx.doi.org/10.1016/j.lfs.2022.120425] [PMID: 35202642]
[15]
Davies, E.R.; Perotin, J.M.; Kelly, J.F.C.; Djukanovic, R.; Davies, D.E.; Haitchi, H.M. Involvement of the epidermal growth factor receptor in IL‐13–mediated corticosteroid‐resistant airway inflammation. Clin. Exp. Allergy, 2020, 50(6), 672-686.
[http://dx.doi.org/10.1111/cea.13591] [PMID: 32096290]
[16]
Ticconi, C.; Pietropolli, A.; Piccione, E. Estrogen replacement therapy and asthma. Pulm. Pharmacol. Ther., 2013, 26(6), 617-623.
[http://dx.doi.org/10.1016/j.pupt.2013.08.004] [PMID: 24035822]
[17]
Xu, W.; Xue, L.; Sun, Y.; Henry, A.; Battle, J.M.; Micault, M.; Morris, S.W. Bcl10 is an essential regulator for A20 gene expression. J. Physiol. Biochem., 2013, 69(4), 821-834.
[http://dx.doi.org/10.1007/s13105-013-0259-2] [PMID: 23677497]
[18]
Liu, H.; Yan, H.; Qu, W.; Wen, X.; Hou, L.; Zhao, W.; Ping, J. Inhibition of thymocyte autophagy-associated CD4+T thymopoiesis is involved in asthma susceptibility in mice exposed to caffeine prenatally. Arch. Toxicol., 2019, 93(5), 1323-1335.
[http://dx.doi.org/10.1007/s00204-019-02418-5] [PMID: 30805671]
[19]
Mostafa, M.M.; Rider, C.F.; Shah, S.; Traves, S.L.; Gordon, P.M.K.; Miller-Larsson, A.; Leigh, R.; Newton, R. Glucocorticoid-driven transcriptomes in human airway epithelial cells: Commonalities, differences and functional insight from cell lines and primary cells. BMC Med. Genomics, 2019, 12(1), 29.
[http://dx.doi.org/10.1186/s12920-018-0467-2] [PMID: 30704470]
[20]
Kodera, Y.; Chiba, H.; Konno, T.; Kohno, T.; Takahashi, H.; Kojima, T. HMGB1-downregulated angulin-1/LSR induces epithelial barrier disruption via claudin-2 and cellular metabolism via AMPK in airway epithelial Calu-3 cells. Biochem. Biophys. Res. Commun., 2020, 527(2), 553-560.
[http://dx.doi.org/10.1016/j.bbrc.2020.04.113] [PMID: 32423802]
[21]
Chen, L.; Zhou, K.; Chen, H.; Li, S.; Lin, D.; Zhou, D. Calcitriol promotes survival of experimental random pattern flap via activation of autophagy. Am. J. Transl. Res., 2017, 9(8), 3642-3653.
[PMID: 28861155]
[22]
Komatsu, M.; Kageyama, S.; Ichimura, Y. p62/SQSTM1/A170: Physiology and pathology. Pharmacol. Res., 2012, 66(6), 457-462.
[http://dx.doi.org/10.1016/j.phrs.2012.07.004] [PMID: 22841931]
[23]
Martin, P.; Diaz-Meco, M.T.; Moscat, J. The signaling adapter p62 is an important mediator of T helper 2 cell function and allergic airway inflammation. EMBO J., 2006, 25(15), 3524-3533.
[http://dx.doi.org/10.1038/sj.emboj.7601250] [PMID: 16874300]

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