Background: Aberrant expression of small non-coding RNAs (sncRNAs), in particular microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) define several pathological processes. Asthma is characterized by airway hyper-reactivity, chronic inflammation and airway wall remodeling. Asthma-specific miRNA profiles were reported for bronchial epithelial cells, whereas sncRNAs expression in asthmatic bronchial smooth muscle (BSM) cells is almost completely unexplored. Objective: To determine whether primary BSM sncRNA expression profile is altered in asthma and identify targets of differentially expressed sncRNAs. Methods: SmallRNA sequencing was used for sncRNA profiling in BSM cells (8 asthma, 6 non-asthma). sncRNA identification and differential expression analysis was performed with iMir. Experimentally validated miRNA targets were identified using Ingenuity Pathway Analysis, putative piRNA targets - with miRanda. Results: Asthmatic BSM cells showed abnormal expression of 32 sncRNAs (26 miRNAs, 5 piRNAs, and 1 snoRNA). 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 may play important roles in the pathophysiology of asthma. Interestingly, 6 of these mRNAs were previously associated with asthma and/or considered as novel therapeutic targets for treatment of this disease. Signaling pathway analysis revealed involvement of 38 miRNA-targeted mRNAs in increased cell proliferation via PTEN and PI3K/Akt signaling pathways. Conclusions: BSM cells of asthma patients are characterized by aberrant sncRNA expression that recapitulates multiple pathological phenotypes of these cells.

Small RNA profiling reveals deregulated PTEN/PI3K/Akt pathway in asthmatic bronchial smooth muscle cells.

ALEXANDROVA, ELENA;HASHIM, ADNAN;NASSA, GIOVANNI;STELLATO , CLAUDIA;WEISZ, Alessandro;
2015

Abstract

Background: Aberrant expression of small non-coding RNAs (sncRNAs), in particular microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) define several pathological processes. Asthma is characterized by airway hyper-reactivity, chronic inflammation and airway wall remodeling. Asthma-specific miRNA profiles were reported for bronchial epithelial cells, whereas sncRNAs expression in asthmatic bronchial smooth muscle (BSM) cells is almost completely unexplored. Objective: To determine whether primary BSM sncRNA expression profile is altered in asthma and identify targets of differentially expressed sncRNAs. Methods: SmallRNA sequencing was used for sncRNA profiling in BSM cells (8 asthma, 6 non-asthma). sncRNA identification and differential expression analysis was performed with iMir. Experimentally validated miRNA targets were identified using Ingenuity Pathway Analysis, putative piRNA targets - with miRanda. Results: Asthmatic BSM cells showed abnormal expression of 32 sncRNAs (26 miRNAs, 5 piRNAs, and 1 snoRNA). 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 may play important roles in the pathophysiology of asthma. Interestingly, 6 of these mRNAs were previously associated with asthma and/or considered as novel therapeutic targets for treatment of this disease. Signaling pathway analysis revealed involvement of 38 miRNA-targeted mRNAs in increased cell proliferation via PTEN and PI3K/Akt signaling pathways. Conclusions: BSM cells of asthma patients are characterized by aberrant sncRNA expression that recapitulates multiple pathological phenotypes of these cells.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11386/4645891
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