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Small RNA profiling reveals deregulated phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway in bronchial smooth muscle cells from asthmatic patients Elena Alexandrova, PhD, Nicola Miglino, PhD, Adnan Hashim, PhD, Giovanni Nassa, PhD, Claudia Stellato, PhD, Michael Tamm, MD, Florent Baty, PhD, Martin Brutsche, MD, PhD, Alessandro Weisz, MD, Pieter Borger, PhD Journal of Allergy and Clinical Immunology Volume 137, Issue 1, Pages (January 2016) DOI: /j.jaci Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 1 sncRNA expression in BSM cells. A, Length distribution of reads in a representative small RNA sequencing library. B, Pie charts showing the percentage of sncRNA species identified in BSM cells of asthmatic patients and healthy subjects. sncRNA shares on the pie charts are indicated clockwise: miRNAs (the biggest share on the both pie charts), piRNAs, transfer RNAs (tRNAs), rRNAs, Rfam, RefGene, transcription initiation RNAs, and others/unassigned sncRNAs. Journal of Allergy and Clinical Immunology , 58-67DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 2 Modulation of sncRNA expression in BSM cells of asthmatic patients versus those of healthy subjects and its effect on cellular processes. A, Heat map. Average expression intensity (log2 of RPM expression values) for differentially expressed sncRNAs identified with a nonparametric Wilcoxon rank sum test (α < .05) and Student t test (P < .05) is shown to the left (blue and yellow). Unsupervised hierarchic clustering of sncRNAs discriminating between BSM cells of healthy subjects and asthmatic patients calculated by using the Pearson correlation coefficient is shown on the right. Each row corresponds to 1 sncRNA, whereas each column corresponds to 1 sample. The data displayed represent the ratio between the RPM value of each sncRNA in a given sample versus the average RPM value for the same sncRNA in all samples. Blue and orange squares on the bottom indicate asthma and control samples, respectively. B, IPA canonical pathway analysis on the list of 38 miRNA-targeted mRNAs. On the horizontal axis, most significantly overrepresented pathways (P < .01) identified are reported, whereas the vertical axis shows the −log10 of the P value calculated based on the Fisher exact test. The ratio reported as orange points represents the numbers of genes in a given pathway that meet cutoff criteria divided by the total numbers of genes that make up that pathway. Journal of Allergy and Clinical Immunology , 58-67DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 3 PTEN signaling pathway deregulation in asthmatic patients. Gene products are compartmentalized in the cell to show their physiologic localization and are represented as nodes with various shapes corresponding to different protein functional classes, as indicated in the legends. Genes expressed and not expressed in BSM cells are shown in blue and white, respectively. Continuous or dashed lines stand for direct or indirect relationship, respectively, whereas blue and gray lines represent active and inactive relationships. Red and green arrows show targeting by upregulated and downregulated sncRNAs, respectively. Potentially perturbed cellular events are shown in yellow. Journal of Allergy and Clinical Immunology , 58-67DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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