title: Small RNA profiling reveals deregulated phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway in bronchial smooth muscle cells from asthmatic patients.
abstract: BACKGROUND
  Aberrant expression of small noncoding RNAs (sncRNAs), microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) in particular, define several pathologic processes. Asthma is characterized by airway hyperreactivity, chronic inflammation, and airway wall remodeling. Asthma-specific miRNA profiles were reported for bronchial epithelial cells, whereas sncRNA expression in asthmatic bronchial smooth muscle (BSM) cells is almost completely unexplored.
  
  
  OBJECTIVE
  We sought to determine whether the primary BSM sncRNA expression profile is altered in asthmatic patients and identify targets of differentially expressed sncRNAs.
  
  
  METHODS
  Small RNA sequencing was used for sncRNA profiling in BSM cells (from 8 asthmatic and 6 nonasthmatic subjects). sncRNA identification and differential expression analysis was performed with iMir software. Experimentally validated miRNA targets were identified by using Ingenuity Pathway Analysis, and putative piRNA targets were identified by using miRanda software.
  
  
  RESULTS
  BSM cells from asthmatic patients showed abnormal expression of 32 sncRNAs (26 miRNAs, 5 piRNAs, and 1 small nucleolar RNA). Target prediction for deregulated miRNAs and piRNAs revealed experimentally validated and predicted mRNA targets expressed in the BSM cells. Thirty-eight of these mRNAs represent major targets for deregulated miRNAs and might play important roles in the pathophysiology of asthma. Interestingly, 6 of these mRNAs were previously associated with asthma, considered as novel therapeutic targets for treatment of this disease, or both. Signaling pathway analysis revealed involvement of 38 miRNA-targeted mRNAs in increased cell proliferation through phosphatase and tensin homolog and phosphoinositide 3-kinase/Akt signaling pathways.
  
  
  CONCLUSIONS
  BSM cells of asthmatic patients are characterized by aberrant sncRNA expression that recapitulates multiple pathologic phenotypes of these cells.
authors.affiliation: Laboratory of Molecular Medicine and Genomics, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy; Genomix4Life Srl, Campus of Medicine, University of Salerno, Baronissi, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Alexandrova
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Nicola
authors.initials: N
authors.lastname: Miglino
authors.affiliation: Laboratory of Molecular Medicine and Genomics, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy.
authors.forename: Adnan
authors.initials: A
authors.lastname: Hashim
authors.affiliation: Laboratory of Molecular Medicine and Genomics, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Nassa
authors.affiliation: Laboratory of Molecular Medicine and Genomics, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Stellato
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Tamm
authors.affiliation: Division of Molecular Pathology and Medical Genomics, Kantonsspital St Gallen, St Gallen, Switzerland.
authors.forename: Florent
authors.initials: F
authors.lastname: Baty
authors.affiliation: Division of Molecular Pathology and Medical Genomics, Kantonsspital St Gallen, St Gallen, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Brutsche
authors.affiliation: Laboratory of Molecular Medicine and Genomics, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy; Molecular Pathology and Medical Genomics Unit, "SS. Giovanni di Dio e Ruggi d'Aragona-Schuola Medica Salernitana" University Hospital, Salerno, Italy. Electronic address: aweisz@unisa.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Weisz
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland. Electronic address: pieter.borger@unibas.ch.
authors.forename: Pieter
authors.initials: P
authors.lastname: Borger
mesh_terms: D001249:Asthma / Q000235:genetics*; D001980:Bronchi / Q000166:cytology; D020869:Gene Expression Profiling; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D058727:RNA, Small Untranslated / Q000235:genetics*; D017423:Sequence Analysis, RNA
chemical_list: D058727:RNA, Small Untranslated; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Small noncoding RNA; asthma; phosphatase and tensin homolog/phosphoinositide 3-kinase/Akt pathway; smooth muscle cells