Elena Alexandrova1, Nicola Miglino2, Adnan Hashim3, Giovanni Nassa3, Claudia Stellato3, Michael Tamm2, Florent Baty4, Martin Brutsche4, Alessandro Weisz5, Pieter Borger6. 1. 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. 2. Department of Biomedicine, University of Basel, Basel, Switzerland. 3. Laboratory of Molecular Medicine and Genomics, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy. 4. Division of Molecular Pathology and Medical Genomics, Kantonsspital St Gallen, St Gallen, Switzerland. 5. 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. 6. Department of Biomedicine, University of Basel, Basel, Switzerland. Electronic address: pieter.borger@unibas.ch.
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.
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: Jiang Li; Ronald Panganiban; Alvin T Kho; Michael J McGeachie; Leanna Farnam; Robert P Chase; Scott T Weiss; Quan Lu; Kelan G Tantisira Journal: Am J Respir Crit Care Med Date: 2020-07-01 Impact factor: 21.405
Authors: Elena Alexandrova; Giovanni Nassa; Giacomo Corleone; Anton Buzdin; Alexander M Aliper; Nadezhda Terekhanova; Denis Shepelin; Alexander Zhavoronkov; Michael Tamm; Luciano Milanesi; Nicola Miglino; Alessandro Weisz; Pieter Borger Journal: Oncotarget Date: 2016-05-03
Authors: J Ong; A Faiz; W Timens; M van den Berge; M M Terpstra; K Kok; A van den Berg; J Kluiver; C A Brandsma Journal: Sci Rep Date: 2019-12-03 Impact factor: 4.379