scholarly journals Mir-608 Overexpression in Idiopathic Pulmonary Fibrosis (IPF) is Related to Acetylcholinesterase Single Nucleotide Polymorphism (SNP)

2020 ◽  
Author(s):  
Gali Epstein Shochet ◽  
Lilach Israeli-Shani ◽  
Isabelle Kains ◽  
Ori Wand ◽  
David Shitrit
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Usual Interstitial Pneumonia ◽  
Nucleotide Polymorphism ◽  
Allele Polymorphism ◽  
Single Nucleotide ◽  
Formalin Fixed Paraffin ◽  
Chronic Progressive Disease ◽  
Formalin Fixed Paraffin Embedded

Abstract Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that causes scarring of the lungs. The disease is associated with the Usual Interstitial Pneumonia (UIP) pattern, which was not yet fully recapitulated by an animal model. Therefore, the disease is considered ‘human specific’. miRNA-608 is a primate specific miRNA with many potential targets, such CdC42 and Interlukin-6 (IL-6) that were previously implicated in IPF pathology. Objective: To test miR-608 expression and its targets in IPF patient samples.Methods: RNA was extracted from Formalin fixed paraffin embedded (FFPE) tissue sections (N=18). miRNA-608 expression and Cdc42 and IL-6 levels were analyzed by qPCR. Acetylcholinesterase (AChE) is another target of miRNA-608. Its' rs17228616 allele has a single-nucleotide polymorphism (SNP) causing weakened miR-608 interaction (C2098A). Thus, DNA was extracted from whole blood samples from 56 subjects with fibrosing interstitial lung disease (ILD) and this region was sequenced for assessment of rs17228616 allele polymorphism.Results: MiR-608 is significantly overexpressed in IPF samples, in comparison with controls (p<0.05). Cdc42 and IL-6 levels were lower in the IPF patient samples compared with control samples (p<0.001 and p<0.05, respectively). The frequency of the rs17228616 minor A-allele was 17/56 (30.4%) with all patients being heterozygous. This result is significant vs. the published Israeli cohort of healthy individuals, which reported 17% prevalence of this allele in healthy control volunteers (p=0.01, OR = 2.1, CI 95% [1.19-3.9]).Conclusion: MiR-608 is overexpressed in IPF patients. While the exact mechanism remains to be discovered, it could potentially promote fibrotic disease.

scholarly journals MiR-608 overexpression in idiopathic pulmonary fibrosis (IPF)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gali Epstein Shochet ◽  
Lilach Israeli-Shani ◽  
Isabelle Kains ◽  
Ori Wand ◽  
David Shitrit
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Usual Interstitial Pneumonia ◽  
Allele Polymorphism ◽  
Single Nucleotide ◽  
Tissue Sections ◽  
Formalin Fixed Paraffin ◽  
Chronic Progressive Disease ◽  
Formalin Fixed Paraffin Embedded ◽  
Healthy Control

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that causes scarring of the lungs. The disease is associated with the usual interstitial pneumonia pattern, which was not yet fully recapitulated by an animal model. Therefore, the disease is considered ‘human specific’. miRNA-608 is a primate specific miRNA with many potential targets, such CdC42 and Interlukin-6 (IL-6) that were previously implicated in IPF pathology. Objective To test miR-608 expression and its targets in IPF patient samples. Methods RNA was extracted from Formalin fixed paraffin embedded tissue sections (N = 18). miRNA-608 and Cdc42 and IL-6 levels were analyzed by qPCR. Acetylcholinesterase (AChE) is another target of miRNA-608. Its’ rs17228616 allele has a single-nucleotide polymorphism causing weakened miR-608 interaction (C2098A). Thus, DNA was extracted from whole blood samples from 56 subjects with fibrosing interstitial lung disease and this region was sequenced for assessment of rs17228616 allele polymorphism. Results miR-608 is significantly overexpressed in IPF samples in comparison with controls (p < 0.05). Cdc42 and IL-6 levels were lower in the IPF patient samples compared with control samples (p < 0.001 and p < 0.05, respectively). The frequency of the rs17228616 minor A-allele was 17/56 (30.4%) with all patients being heterozygous. This result is significant vs. the published Israeli cohort of healthy individuals, which reported 17% prevalence of this allele in healthy control volunteers (p = 0.01, OR = 2.1, CI 95% [1.19–3.9]). Conclusion miR-608 is overexpressed in IPF patients. While the exact mechanism remains to be discovered, it could potentially promote fibrotic disease.

Detection of Chromosomal Aberrations in Renal Tumors: A Comparative Study of Conventional Cytogenetics and Virtual Karyotyping With Single-Nucleotide Polymorphism Microarrays

2009 ◽  
Vol 133 (12) ◽  
pp. 1917-1922
Author(s):  
Federico A. Monzon ◽  
Karla Alvarez ◽  
Zoran Gatalica ◽  
Julia A. Bridge ◽  
Marilu Nelson ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Renal Tumors ◽  
Complete Agreement ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Epithelial Neoplasms ◽  
Conventional Cytogenetics ◽  
Formalin Fixed

Abstract Context.—Renal epithelial neoplasms have characteristic chromosomal imbalances, and we have shown previously that virtual karyotypes derived from single-nucleotide polymorphism microarrays can be performed on formalin-fixed, paraffin-embedded tissue. Objective.—To perform a direct comparison of virtual and conventional karyotypes to evaluate concordance of results. Design.—Twenty archival formalin-fixed, paraffin-embedded tumor samples with preexisting, conventional cytogenetic results were analyzed with Affymetrix 10K 2.0 or 250K Nsp single-nucleotide polymorphism microarrays. Results.—Nineteen samples yielded adequate virtual karyotypes for interpretation. Eight samples showed complete agreement between the 2 techniques, and 8 samples showed partial agreement. The disease-defining lesions (eg, loss of 3p for clear cell carcinoma) were identified in all 19 cases by virtual karyotypes and in 15 cases by conventional karyotypes. Virtual and conventional karyotypic findings were concordant in the identification of these disease-defining lesions in 86% (13 of 15) of cases. In 3 cases, virtual karyotypes identified lesions consistent with the morphologic diagnosis, whereas the conventional karyotypes were unsuccessful because of insufficient tumor representation or stromal overgrowth. Two cases with acquired uniparental disomy were identified by single-nucleotide polymorphism arrays, and 5 cases with translocations were identified by conventional karyotype. Conclusions.—Our results show that both techniques are able to identify the characteristic chromosomal abnormality for renal tumor subtypes in most cases. Discrepancies can be explained by inherent limitations of each technique, inadequate tumor sampling, and tumor heterogeneity. We conclude that virtual karyotyping is a robust alternative to conventional cytogenetics for the evaluation of chromosomal anomalies in formalin-fixed, paraffin-embedded tissues from renal epithelial neoplasms.

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