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

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,

Research advances in molecular mechanisms underlying the pathogenesis of cystic fibrosis: From technical improvement to clinical applications (Review)

“…Moreover, as chronic bacterial lung infection is a major cause of CF morbidity, exhaled breath condensate was used for miRNA profile analysis of patients with CF with microbial infection. The results demonstrated that 6 miRNAs (has-miRNA-432-5p, hsa-miRNA-3170, hsa-miR449c, hsa-miR-1276, hsa-miR-1247 and hsa-miR-548) were identified as potential biomarkers for patients with CF and chronic Pseudomonas infection (62). These reports indicated that miRNAs serve crucial functions in the pathogenesis of CF and are key diagnosis and prognosis markers for CF.…”

“…Identification of the microorganism in patients with CF guides the path for subsequent antibiotic therapy (93). As mentioned in previous sections, microorganism detection can be performed by analyzing the expression profile of miRNAs (62) or other novel biomarkers (63). Therefore, traditional PCR analysis, microarray methods and NGS are capable of biomarkers profiling.…”

Fucoxanthin may inhibit cervical cancer cell proliferation via downregulation of HIST1H3D

“…34 In addition, HIST1H3D may be involved in the process of cystic fibrosis. 35 Histone family members play an important role in chromatin condensation and cell cycle progression. 28 Histones are abnormally expressed in tumours and contribute to the pathogenesis of various malignancies.…”

“… 32 Methylated H3.1 has been shown to be associated with gene-silencing and heterochromatin formation, 33 and HIST1H3D is reported to be elevated in tumour necrosis factor (TNF)-α-induced endothelial cell inflammation and lung disease involving pseudomonas infection. 34 , 35 Furthermore, HIST1H3D expression is shown to be upregulated in tumour tissues, such as lung cancer and primary gastric cancer tissues. 36 , 37 …”

“…32 Methylated H3.1 has been shown to be associated with gene-silencing and heterochromatin formation, 33 and HIST1H3D is reported to be elevated in tumour necrosis factor (TNF)a-induced endothelial cell inflammation and lung disease involving pseudomonas infection. 34,35 Furthermore, HIST1H3D expression is shown to be upregulated in tumour tissues, such as lung cancer and primary gastric cancer tissues. 36,37 The aim of the present study was to investigate the roles of fucoxanthin and HIST1H3D in cervical cancer through investigation of genes that are differentially expressed between cervical cancer cells treated with fucoxanthin and untreated cells, and the effect of HIST1H3D expression on cervical cancer cell activity.…”