Altered circular RNA expression profiles in an ovalbumin-induced murine model of allergic rhinitis

Main Article Content

Jie Chen
Xiyan Xiao
Shan He
Yi Qiao
Shuwei Ma

Keywords

allergic rhinitis, circular RNA, RNA sequencing, bioinformatics, murine model

Abstract

Background: Emerging evidence shows that circular RNAs (circRNAs) participate in the pathogenesis of multiple immune diseases. However, few studies have focused on the mechanisms of circRNAs involved in allergic rhinitis (AR).


Methods: This study performed an RNA sequence (RNA-seq) profiling to identify the expression of circRNAs in nasal mucosa from ovalbumin-induced AR murine models and normal controls. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) was then conducted to validate the differential expression of circRNAs. Bioinformatics analysis was applied to demonstrate the biological functions of the dysregulated circRNAs.


Results: A total of 86 distinct circRNA candidates were sequenced, of which 51 were upregulated and 35 were downregulated. The T cell receptor, B cell receptor, and calcium signaling pathways may be involved in the pathology of AR. Furthermore, a circRNA-miRNA interaction network was constructed via miRNA response elements analysis. Some circRNAs were cor-related with miRNAs that are involved in T cell polarization and activation, thereby highlighting their potential role in the pathogenesis of AR.


Conclusions: This study demonstrates a number of aberrantly expressed circRNAs related to AR, and offers a novel perspective into AR pathogenesis and future therapeutic strategies.

Abstract 99 | PDF Downloads 69 XML Downloads 0 HTML Downloads 0

References

1. Meltzer EO. Allergic rhinitis: Burden of illness, quality of life, comorbidities, and control. Immunol Allergy Clin North Am. 2016;36:235–48. https://doi.org/10.1016/j.iac.2015.12.002

2. Zhang Y, Zhang L. Increasing prevalence of allergic rhinitis in China. Allergy Asthma Immunol Res. 2019;11:156–69. https:// doi.org/10.4168/aair.2019.11.2.156

3. Bozek A, Scierski W, Ignasiak B, Jarzab J, Misiolek M. The prevalence and characteristics of local allergic rhinitis in Poland. Rhinology. 2019;57:213–18. https://doi.org/10.4193/ Rhin18.137

4. Eifan AO, Durham SR. Pathogenesis of rhinitis. Clin Exp Allergy. 2016;46:1139–51. https://doi.org/10.1111/cea.12780

5. Cox L. Approach to patients with allergic rhinitis: Testing and treatment. Med Clin North Am. 2020;104:77–94. https://doi. org/10.1016/j.mcna.2019.09.001

6. Zhang XO, Dong R, Zhang Y, Zhang JL, Luo Z, Zhang J, et al. Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. Genome Res. 2016;26:1277–87. https:// doi.org/10.1101/gr.202895.115

7. Lei B, Tian Z, Fan W, Ni B. Circular RNA: A novel biomarker and therapeutic target for human cancers. Int J Med Sci. 2019;16:292–301. https://doi.org/10.7150/ijms.28047

8. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495:384–8. https://doi. org/10.1038/nature11993

9. Pamudurti NR, Bartok O, Jens M, Ashwal-Fluss R, Stottmeister C, Ruhe L, et al. Translation of circRNAs. Mol Cell. 2017;66:9– 21.e7. https://doi.org/10.1016/j.molcel.2017.02.021

10. Huang Z, Cao Y, Zhou M, Qi X, Fu B, Mou Y, et al. Hsa_ circ_0005519 increases IL-13/IL-6 by regulating hsa-let-7a-5p in CD4(+) T cells to affect asthma. Clin Exp Allergy. 2019;49:1116– 27. https://doi.org/10.1111/cea.13445

11. Zhang Y, Zhang Y, Li X, Zhang M, Lv K. Microarray analysis of circular RNA expression patterns in polarized macrophages. Int J Mol Med. 2017;39:373–9. https://doi.org/10.3892/ijmm.2017.2852

12. Wang YH, Yu XH, Luo SS, Han H. Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell ageing. Immun Ageing. 2015;12:17. https://doi.org/10.1186/s12979-015-0042-z

13. Agirre X, Meydan C, Jiang Y, Garate L, Doane AS, Li Z, et al. Long non-coding RNAs discriminate the stages and gene regulatory states of human humoral immune response. Nat Commun. 2019;10:821. https://doi.org/10.1038/s41467-019-08679-z

14. Li H, Li K, Lai W, Li X, Wang H, Yang J, et al. Comprehensive circular RNA profiles in plasma reveals that circular RNAs can be used as novel biomarkers for systemic lupus erythematosus. Clin Chim Acta. 2018;480:17–25. https://doi.org/10.1016/j. cca.2018.01.026

15. Ouyang Q, Wu J, Jiang Z, Zhao J, Wang R, Lou A, et al. Microarray expression profile of circular RNAs in peripheral blood mononuclear cells from rheumatoid arthritis patients. Cell Physiol Biochem. 2017;42:651–9. https://doi. org/10.1159/000477883

16. Iparraguirre L, Muñoz-Culla M, Prada-Luengo I, Castillo-Triviño T, Olascoaga J, Otaegui D. Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis. Hum Mol Genet. 2017;26:3564–72. https:// doi.org/10.1093/hmg/ddx243

17. Luo Y, Deng Y, Tao Z, Chen S, Xiao B, Ren J, et al. Regulatory effect of microRNA-135a on the Th1/Th2 imbalance in a murine model of allergic rhinitis. Exp Ther Med. 2014;8:1105– 10. https://doi.org/10.3892/etm.2014.1855

18. Teng Y, Zhang R, Liu C, Zhou L, Wang H, Zhuang W, et al. miR-143 inhibits interleukin-13-induced inflammatory cytokine and mucus production in nasal epithelial cells from allergic rhinitis patients by targeting IL13Rα1. Biochem Biophys Res Commun. 2015;457:58–64. https://doi.org/10.1016/j. bbrc.2014.12.058

19. Chen Z, Deng Y, Li F, Xiao B, Zhou X, Tao Z. MicroRNA-466a-3p attenuates allergic nasal inflammation in mice by target-ing GATA3. Clin Exp Immunol. 2019;197:366–75. https://doi. org/10.1111/cei.13312

20. Gagliani N, Huber S. Basic aspects of T helper cell differentiation. Methods Mol Biol. 2017;1514:19–30. https://doi. org/10.1007/978-1-4939-6548-9_2

21. Steelant B, Seys SF, Van Gerven L, Van Woensel M, Farré R, Wawrzyniak P, et al. Histamine and T helper cytokine-driven epithelial barrier dysfunction in allergic rhinitis. J Allergy Clin Immunol. 2018;141:951–63.e8. https://doi.org/10.1016/j. jaci.2017.08.039

22. Huang W, August A. The signaling symphony: T cell receptor tunes cytokine-mediated T cell differentiation. J Leukoc Biol. 2015;97:477–85. https://doi.org/10.1189/jlb.1RI0614-293R

23. Rawlings DJ, Metzler G, Wray-Dutra M, Jackson SW. Altered B cell signalling in autoimmunity. Nat Rev Immunol. 2017;17:421– 36. https://doi.org/10.1038/nri.2017.24

24. Trebak M, Kinet JP. Calcium signalling in T cells. Nat Rev Immunol. 2019;19:154–69. https://doi.org/10.1038/s41577-018-0110-7

25. Hemon P, Renaudineau Y, Debant M, Le Goux N, Mukherjee S, Brooks W, et al. Calcium signaling: From normal B cell development to tolerance breakdown and autoimmunity. Clin Rev Allergy Immunol. 2017;53:141–65. https://doi.org/10.1007/ s12016-017-8607-6

26. Sakai H, Hara T, Todoroki K, Igarashi Y, Misawa M, Narita M, et al. Elevated guanylate cyclase and cyclic-guanosine mono-phosphate-dependent protein kinase levels in nasal mucosae of antigen-challenged rats. Microvasc Res. 2013;90:150–3. https://doi.org/10.1016/j.mvr.2013.08.009

27. Gao Y, Yu Z. MicroRNA- 16 inhibits interleukin- 13- induced inflammatory cytokine secretion and mucus production in nasal epithelial cells by suppressing the IκB kinase β/nuclear factor- κB pathway. Mol Med Rep. 2018;18:4042–50. https:// doi.org/10.3892/mmr.2018.9394

28. Xiao L, Jiang L, Hu Q, Li Y. MicroRNA-133b ameliorates allergic inflammation and symptom in murine model of allergic rhinitis by targeting Nlrp3. Cell Physiol Biochem. 2017;42:901–12. https://doi.org/10.1159/000478645

29. Wang T, Chen D, Wang P, Xu Z, Li Y. miR-375 prevents nasal mucosa cells from apoptosis and ameliorates allergic rhinitis via inhibiting JAK2/STAT3 pathway. Biomed Pharmacother. 2018;103:621–7. https://doi.org/10.1016/j. biopha.2018.04.050