Integrated miRNA and mRNA expression profiling reveals dysregulated miRNA-mRNA regulatory networks in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps

Xiangting Bu; Ming Wang; Ge Luan; Yang Wang; Chengshuo Wang; Luo Zhang

doi:10.1002/alr.22781

Integrated miRNA and mRNA expression profiling reveals dysregulated miRNA-mRNA regulatory networks in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps

Int Forum Allergy Rhinol. 2021 Aug;11(8):1207-1219. doi: 10.1002/alr.22781. Epub 2021 Feb 21.

Authors

Xiangting Bu^{1

2}, Ming Wang^{1

2}, Ge Luan^{1

2}, Yang Wang^{1

2}, Chengshuo Wang^{1

2}, Luo Zhang^{1

2

3}

Affiliations

¹ Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China.
² Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China.
³ Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China.

PMID: 33611865
DOI: 10.1002/alr.22781

Abstract

Background: The precise mechanisms underlying pathogenesis of different subtypes of chronic rhinosinusitis with nasal polyps (CRSwNP) are still unclear. Emerging evidence indicates that microRNAs may play a role in the pathogenesis of CRSwNP. This study aimed to identify the dysregulated microRNA-messenger RNA (miRNA-mRNA) regulatory networks in eosinophilic (E) and non-eosinophilic (non-E) CRSwNP.

Methods: Whole-transcriptome sequencing was performed on nasal tissues of patients with ECRSwNP and non-ECRSwNP, and control subjects. An integrated analysis of miRNA and mRNA expression was conducted to identify key mRNAs and miRNAs involved in the pathogenesis of ECRSwNP and non-ECRSwNP. The miRNAs of interest and their target genes were validated using quantitative real-time polymerase chain reaction (PCR).

Results: A group of differentially expressed mRNAs (DE-mRNAs) and miRNAs (DE-miRs) were identified in ECRSwNP patients vs control subjects, non-ECRSwNP patients vs control subjects, and non-ECRSwNP vs ECRSwNP patients, respectively. Pathway enrichment analysis showed distinct immune and inflammatory functions associated with DE-mRNAs and target genes of DE-miRs in ECRSwNP vs control and non-ECRSwNP vs control groups. The miRNA-mRNA regulatory networks constructed with Cytoscape highlighted the roles of miR-154, miR-221, and miR-223 family miRNAs relating to both ECRSwNP and non-ECRSwNP, and the roles of the let-7 and miR-34/449 families in the development of non-ECRSwNP. Assessment using real-time PCR for the expression of miRNAs and target genes demonstrated highly consistent data with the RNA sequencing data.

Conclusion: ECRSwNP and non-ECRSwNP patients express distinct miRNA-mRNA regulatory networks compared with control subjects, thus providing potential targets for future development of novel therapeutic approaches for the management of CRSwNP.

Keywords: chronic rhinosinusitis with nasal polyps; eosinophilic/noneosinophilic chronic rhinosinusitis with nasal polyps; integrate analysis; mRNA; microRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chronic Disease
Eosinophils / pathology
Humans
MicroRNAs* / genetics
Nasal Polyps* / genetics
Nasal Polyps* / pathology
RNA, Messenger / genetics
Rhinitis* / genetics
Rhinitis* / pathology

Substances

MIRN154 microRNA, human
MicroRNAs
RNA, Messenger