The role of microRNAs in chronic pseudomonas lung infection in Cystic fibrosis

Katherine Fesen, Patricia Silveyra, Nathalie Fuentes, Marvin Nicoleau, Lidys Rivera, Diane Kitch, Gavin Graff, Roopa Siddaiah

Research output: Contribution to journalArticle

Abstract

Background: Cystic Fibrosis (CF) is the most common life limiting genetic disorder, characterized by chronic respiratory failure secondary to inflammation and chronic bacterial lung infection. Pseudomonas aeruginosa lung infection is associated with more severe lung disease and rapid progression of respiratory failure when compared to Staphylococcus aureus infection. We hypothesized that a specific signature of epigenetic factors targeting specific gene transcripts contributes to the increased morbidity seen in CF patients with chronic Pseudomonas infection. Methods: We collected exhaled breath condensate (EBC) from 27 subjects and evaluated miRNA signatures in these samples using commercial PCR array. We identified predicted mRNA targets and associated signaling pathways using Ingenuity Pathway Analysis. Results: We found 11 differentially expressed miRNAs in EBC of patients infected with Pseudomonas aeruginosa compared to EBC from CF patients who were not chronically infected with Pseudomonas aeruginosa (p < 0.05). Six of these miRNAs (hsa-miRNA-1247, hsa-miRNA-1276, hsa-miRNA-449c, hsa-miRNA-3170, hsa-miRNA-432-5p and hsa-miR-548) were significantly different in the CF Pseudomonas positive group when compared to both the CF Pseudomonas negative group and healthy control group. Ingenuity pathway analysis (IPA) revealed organismal injury and abnormalities, reproductive system disease and cancer as the top diseases and bio functions associated with these miRNAs. IPA also detected RELA, JUN, TNF, IL-10, CTNNB1, IL-13, SERPINB8, CALM1, STARD3NL, SFI1, CD55, RPS6KA4, TTC36 and HIST1H3D as the top target genes for these miRNAs. Conclusion: Our study identified 6 miRNAs as epigenetic factors specifically associated with chronic Pseudomonas infection in patients with CF.

Original languageEnglish (US)
Pages (from-to)133-138
Number of pages6
JournalRespiratory Medicine
Volume151
DOIs
StatePublished - May 1 2019

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Pseudomonas Infections
MicroRNAs
Cystic Fibrosis
Lung
Pseudomonas aeruginosa
Pseudomonas
Epigenomics
Respiratory Insufficiency
Inborn Genetic Diseases
Interleukin-13
Gene Targeting
Infection
Bacterial Infections
Interleukin-10
Lung Diseases
Disease Progression
Staphylococcus aureus

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

Cite this

Fesen, Katherine ; Silveyra, Patricia ; Fuentes, Nathalie ; Nicoleau, Marvin ; Rivera, Lidys ; Kitch, Diane ; Graff, Gavin ; Siddaiah, Roopa. / The role of microRNAs in chronic pseudomonas lung infection in Cystic fibrosis. In: Respiratory Medicine. 2019 ; Vol. 151. pp. 133-138.
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abstract = "Background: Cystic Fibrosis (CF) is the most common life limiting genetic disorder, characterized by chronic respiratory failure secondary to inflammation and chronic bacterial lung infection. Pseudomonas aeruginosa lung infection is associated with more severe lung disease and rapid progression of respiratory failure when compared to Staphylococcus aureus infection. We hypothesized that a specific signature of epigenetic factors targeting specific gene transcripts contributes to the increased morbidity seen in CF patients with chronic Pseudomonas infection. Methods: We collected exhaled breath condensate (EBC) from 27 subjects and evaluated miRNA signatures in these samples using commercial PCR array. We identified predicted mRNA targets and associated signaling pathways using Ingenuity Pathway Analysis. Results: We found 11 differentially expressed miRNAs in EBC of patients infected with Pseudomonas aeruginosa compared to EBC from CF patients who were not chronically infected with Pseudomonas aeruginosa (p < 0.05). Six of these miRNAs (hsa-miRNA-1247, hsa-miRNA-1276, hsa-miRNA-449c, hsa-miRNA-3170, hsa-miRNA-432-5p and hsa-miR-548) were significantly different in the CF Pseudomonas positive group when compared to both the CF Pseudomonas negative group and healthy control group. Ingenuity pathway analysis (IPA) revealed organismal injury and abnormalities, reproductive system disease and cancer as the top diseases and bio functions associated with these miRNAs. IPA also detected RELA, JUN, TNF, IL-10, CTNNB1, IL-13, SERPINB8, CALM1, STARD3NL, SFI1, CD55, RPS6KA4, TTC36 and HIST1H3D as the top target genes for these miRNAs. Conclusion: Our study identified 6 miRNAs as epigenetic factors specifically associated with chronic Pseudomonas infection in patients with CF.",
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The role of microRNAs in chronic pseudomonas lung infection in Cystic fibrosis. / Fesen, Katherine; Silveyra, Patricia; Fuentes, Nathalie; Nicoleau, Marvin; Rivera, Lidys; Kitch, Diane; Graff, Gavin; Siddaiah, Roopa.

In: Respiratory Medicine, Vol. 151, 01.05.2019, p. 133-138.

Research output: Contribution to journalArticle

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T1 - The role of microRNAs in chronic pseudomonas lung infection in Cystic fibrosis

AU - Fesen, Katherine

AU - Silveyra, Patricia

AU - Fuentes, Nathalie

AU - Nicoleau, Marvin

AU - Rivera, Lidys

AU - Kitch, Diane

AU - Graff, Gavin

AU - Siddaiah, Roopa

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N2 - Background: Cystic Fibrosis (CF) is the most common life limiting genetic disorder, characterized by chronic respiratory failure secondary to inflammation and chronic bacterial lung infection. Pseudomonas aeruginosa lung infection is associated with more severe lung disease and rapid progression of respiratory failure when compared to Staphylococcus aureus infection. We hypothesized that a specific signature of epigenetic factors targeting specific gene transcripts contributes to the increased morbidity seen in CF patients with chronic Pseudomonas infection. Methods: We collected exhaled breath condensate (EBC) from 27 subjects and evaluated miRNA signatures in these samples using commercial PCR array. We identified predicted mRNA targets and associated signaling pathways using Ingenuity Pathway Analysis. Results: We found 11 differentially expressed miRNAs in EBC of patients infected with Pseudomonas aeruginosa compared to EBC from CF patients who were not chronically infected with Pseudomonas aeruginosa (p < 0.05). Six of these miRNAs (hsa-miRNA-1247, hsa-miRNA-1276, hsa-miRNA-449c, hsa-miRNA-3170, hsa-miRNA-432-5p and hsa-miR-548) were significantly different in the CF Pseudomonas positive group when compared to both the CF Pseudomonas negative group and healthy control group. Ingenuity pathway analysis (IPA) revealed organismal injury and abnormalities, reproductive system disease and cancer as the top diseases and bio functions associated with these miRNAs. IPA also detected RELA, JUN, TNF, IL-10, CTNNB1, IL-13, SERPINB8, CALM1, STARD3NL, SFI1, CD55, RPS6KA4, TTC36 and HIST1H3D as the top target genes for these miRNAs. Conclusion: Our study identified 6 miRNAs as epigenetic factors specifically associated with chronic Pseudomonas infection in patients with CF.

AB - Background: Cystic Fibrosis (CF) is the most common life limiting genetic disorder, characterized by chronic respiratory failure secondary to inflammation and chronic bacterial lung infection. Pseudomonas aeruginosa lung infection is associated with more severe lung disease and rapid progression of respiratory failure when compared to Staphylococcus aureus infection. We hypothesized that a specific signature of epigenetic factors targeting specific gene transcripts contributes to the increased morbidity seen in CF patients with chronic Pseudomonas infection. Methods: We collected exhaled breath condensate (EBC) from 27 subjects and evaluated miRNA signatures in these samples using commercial PCR array. We identified predicted mRNA targets and associated signaling pathways using Ingenuity Pathway Analysis. Results: We found 11 differentially expressed miRNAs in EBC of patients infected with Pseudomonas aeruginosa compared to EBC from CF patients who were not chronically infected with Pseudomonas aeruginosa (p < 0.05). Six of these miRNAs (hsa-miRNA-1247, hsa-miRNA-1276, hsa-miRNA-449c, hsa-miRNA-3170, hsa-miRNA-432-5p and hsa-miR-548) were significantly different in the CF Pseudomonas positive group when compared to both the CF Pseudomonas negative group and healthy control group. Ingenuity pathway analysis (IPA) revealed organismal injury and abnormalities, reproductive system disease and cancer as the top diseases and bio functions associated with these miRNAs. IPA also detected RELA, JUN, TNF, IL-10, CTNNB1, IL-13, SERPINB8, CALM1, STARD3NL, SFI1, CD55, RPS6KA4, TTC36 and HIST1H3D as the top target genes for these miRNAs. Conclusion: Our study identified 6 miRNAs as epigenetic factors specifically associated with chronic Pseudomonas infection in patients with CF.

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Fesen K, Silveyra P, Fuentes N, Nicoleau M, Rivera L, Kitch D et al. The role of microRNAs in chronic pseudomonas lung infection in Cystic fibrosis. Respiratory Medicine. 2019 May 1;151:133-138. https://doi.org/10.1016/j.rmed.2019.04.012