MiR-608 overexpression in idiopathic pulmonary fibrosis (IPF).


Journal

BMC pulmonary medicine
ISSN: 1471-2466
Titre abrégé: BMC Pulm Med
Pays: England
ID NLM: 100968563

Informations de publication

Date de publication:
05 Jan 2021
Historique:
received: 21 10 2020
accepted: 09 12 2020
entrez: 6 1 2021
pubmed: 7 1 2021
medline: 7 9 2021
Statut: epublish

Résumé

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. To test miR-608 expression and its targets in IPF patient samples. 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. 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]). miR-608 is overexpressed in IPF patients. While the exact mechanism remains to be discovered, it could potentially promote fibrotic disease.

Sections du résumé

BACKGROUND 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 OBJECTIVE
To test miR-608 expression and its targets in IPF patient samples.
METHODS 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 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 CONCLUSIONS
miR-608 is overexpressed in IPF patients. While the exact mechanism remains to be discovered, it could potentially promote fibrotic disease.

Identifiants

pubmed: 33402146
doi: 10.1186/s12890-020-01377-3
pii: 10.1186/s12890-020-01377-3
pmc: PMC7786457
doi:

Substances chimiques

GPI-Linked Proteins 0
IL6 protein, human 0
Interleukin-6 0
MIRN608 microRNA, human 0
MicroRNAs 0
ACHE protein, human EC 3.1.1.7
Acetylcholinesterase EC 3.1.1.7
CDC42 protein, human EC 3.6.5.2
cdc42 GTP-Binding Protein EC 3.6.5.2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1

Références

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Auteurs

Gali Epstein Shochet (G)

Pulmonary Department, Meir Medical Center, 59 Tchernichovsky St., 44281, Kfar Saba, Israel. gali.epstein@clalit.org.il.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. gali.epstein@clalit.org.il.

Lilach Israeli-Shani (L)

Pulmonary Department, Meir Medical Center, 59 Tchernichovsky St., 44281, Kfar Saba, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Isabelle Kains (I)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Ori Wand (O)

Pulmonary Department, Meir Medical Center, 59 Tchernichovsky St., 44281, Kfar Saba, Israel.

David Shitrit (D)

Pulmonary Department, Meir Medical Center, 59 Tchernichovsky St., 44281, Kfar Saba, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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