title: Altered microRNA Expression Profiles of Extracellular Vesicles in Nasal Mucus From Patients With Allergic Rhinitis.
abstract: OBJECTIVE
  Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Exosomes or extracellular vesicles are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in allergic diseases. In this study, we characterized the microRNA (miRNA) content of exosomes in AR.
  
  
  METHODS
  Extracellular vesicles were isolated from nasal mucus from healthy control subjects (n=10) and patients with severe AR (n=10). Vesicle RNA was analyzed by using a TaqMan microRNA assays Human Panel-Early Access kit (Applied Biosystems, Foster City, CA, USA) containing probes for 366 human miRNAs, and selected findings were validated with quantitative RT-PCR. Target prediction and pathway analysis for the differentially expressed miRNAs were performed using DIANA-mirPath.
  
  
  RESULTS
  Twenty-one vesicle miRNAs were up-regulated and 14 miRNAs were under-regulated significantly (P<0.05) in nasal mucus from AR patients when compared to healthy controls. Bioinformatic analysis by DIANA-mirPath demonstrated that 32 KEGG biological processes were significantly enriched (P<0.05, FDR corrected) among differentially expressed vesicle miRNA signatures. Among them, the B-cell receptor signaling pathway (P=3.709E-09), the natural killer cell-mediated cytotoxicity (P=8.466E-05), the T-cell receptor signaling pathway (P=0.00075), the RIG-I-like receptor signaling pathway (P=0.00127), the Wnt signaling pathway (P=0.00130), endocytosis (P=0.00440), and salivary secretion (P=0.04660) were the most prominent pathways enriched in quantiles with differential vesicle miRNA patterns. Furthermore, miR-30-5p, miR-199b-3p, miR-874, miR-28-3p, miR-203, and miR-875-5p, involved in B-cell receptor and salivary secretion signaling pathways, were selected for validation using independent samples from 44 AR patients and 20 healthy controls. MiR-30-5p and miR-199b-3p were significantly increased in extracellular vesicles from nasal mucus when compared to healthy controls, while miR-874 and miR-28-3p were significantly down-regulated. In addition, miRNA-203 was significantly increased in AR patients, while miRNA-875-5p was found to be significantly decreased in AR patients.
  
  
  CONCLUSIONS
  This study demonstrated that vesicle miRNA may be a regulator for the development of AR.
authors.affiliation: Department of Otolaryngology, First People Hospital of Zhangjiagang City, Suzhou, China. Gordon-wu@qq.com.
authors.forename: Geping
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Guanghai
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai, China.
authors.forename: Ruxin
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience and Department of Neurobiology and Psychology, Key lab of Pain Research and Therapy, Soochow University, Suzhou, China.
authors.forename: Guangyin
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Science and Education, First People Hospital of Zhangjiagang City, Suzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Wen
authors.affiliation: Department of Otolaryngology, First People Hospital of Zhangjiagang City, Suzhou, China.
authors.forename: Jianbing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Otolaryngology, First People Hospital of Zhangjiagang City, Suzhou, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, First People Hospital of Zhangjiagang City, Suzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
keywords: Extracellular vesicles; allergic rhinitis; microRNAs