Non-coding RNA in cystic fibrosis

Glasgow, Arlene; Santi, Chiara De; Greene, Catherine M.

doi:10.1042/bst20170469

Cited by 35 publications

(27 citation statements)

References 91 publications

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“…miR-221 is increased in CF bronchial brushings, whilst its target, activating transcription factor 6 (ATF6; a transcription factor involved in the UPR), is decreased [138]. The role of dysregulated miRNAs in CF and other lung diseases has been more extensively reviewed elsewhere, for example Glasgow et al [139] and Dutta et al [140].…”

Section: Mirnas In Cfmentioning

confidence: 99%

Alpha-1 Antitrypsin—A Target for MicroRNA-Based Therapeutic Development for Cystic Fibrosis

Hunt

Glasgow

Humphreys

et al. 2020

IJMS

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Cystic fibrosis (CF) is an autosomal recessive genetic disorder arising from mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Disruption to normal ion homeostasis in the airway results in impaired mucociliary clearance, leaving the lung more vulnerable to recurrent and chronic bacterial infections. The CF lung endures an excess of neutrophilic inflammation, and whilst neutrophil serine proteases are a crucial part of the innate host defence to infection, a surplus of neutrophil elastase (NE) is understood to create a net destructive effect. Alpha-1 antitrypsin (A1AT) is a key antiprotease in the control of NE protease activity but is ineffective in the CF lung due to the huge imbalance of NE levels. Therapeutic strategies to boost levels of protective antiproteases such as A1AT in the lung remain an attractive research strategy to limit the damage from excess protease activity. microRNAs are small non-coding RNA molecules that bind specific cognate sequences to inhibit expression of target mRNAs. The inhibition of miRNAs which target the SERPINA1 (A1AT-encoding gene) mRNA represents a novel therapeutic approach for CF inflammation. This could involve the delivery of antagomirs that bind and sequester the target miRNA, or target site blockers that bind miRNA recognition elements within the target mRNA to prevent miRNA interaction. Therefore, miRNA targeted therapies offer an alternative strategy to drive endogenous A1AT production and thus supplement the antiprotease shield of the CF lung.

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Section: Mirnas In Cfmentioning

confidence: 99%

Alpha-1 Antitrypsin—A Target for MicroRNA-Based Therapeutic Development for Cystic Fibrosis

Hunt

Glasgow

Humphreys

et al. 2020

IJMS

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“… 1 ncRNAs can be classified by length (small, 18–200 nt; long, >200 nt) or by function (housekeeping ncRNAs and regulatory ncRNAs), with research over the last two decades largely focusing on regulatory ncRNAs. 2 miRNAs, which are ∼22 nt long, are the most widely studied class of regulatory ncRNAs, and these molecules mediate post-transcriptional gene silencing in animals by controlling the translation of mRNAs into proteins. 3 lncRNAs, longer than 200 nt, are another subtype of regulatory ncRNAs that have a broad repertoire of functions in chromatin modification as well as in transcriptional, post-transcriptional, and translational regulation.…”

Section: Main Textmentioning

confidence: 99%

“… 3 lncRNAs, longer than 200 nt, are another subtype of regulatory ncRNAs that have a broad repertoire of functions in chromatin modification as well as in transcriptional, post-transcriptional, and translational regulation. 2 , 3 …”

Section: Main Textmentioning

confidence: 99%

Potential Regulatory Roles of MicroRNAs and Long Noncoding RNAs in Anticancer Therapies

Xie

et al. 2018

Molecular Therapy - Nucleic Acids

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MicroRNAs and long noncoding RNAs have long been investigated due to their roles as diagnostic and prognostic biomarkers of cancers and regulators of tumorigenesis, and the potential regulatory roles of these molecules in anticancer therapies are attracting increasing interest as more in-depth studies are performed. The major clinical therapies for cancer include chemotherapy, immunotherapy, and targeted molecular therapy. MicroRNAs and long noncoding RNAs function through various mechanisms in these approaches, and the mechanisms involve direct targeting of immune checkpoints, cooperation with exosomes in the tumor microenvironment, and alteration of drug resistance through regulation of different signaling pathways. Herein we review the regulatory functions and significance of microRNAs and long noncoding RNAs in three anticancer therapies, especially in targeted molecular therapy, and their mechanisms.

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“…We, and others, have previously shown that numerous miRNAs are differentially expressed in the lungs of CF adults 14,22,23 . The aim of this study was to investigate whether plasma microRNA expression profiles differ between the sexes in children with CF.…”

Section: Discussionmentioning

confidence: 76%

“…Many miRNAs have been shown to be dysregulated in the CF lung environment, including those with targets such as CFTR, IL-8, Target of Myb1 (TOM1) and activating transcription factor 6 (ATF6), as reviewed by Glasgow et al 14 . In this work, we sought to explore the circulating miRNA profile of paediatric CF plasma.…”

mentioning

confidence: 99%

Plasma microRNA levels in male and female children with cystic fibrosis

Mooney

McKiernan

Raoof

et al. 2020

Sci Rep

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A gender gap exists in cystic fibrosis (CF). Here we investigate whether plasma microRNA expression profiles differ between the sexes in CF children. MicroRNA expression was quantified in paediatric CF plasma (n = 12; six females; Age range:1-6; Median Age: 3; 9 p.Phe508del homo-or heterozygotes) using TaqMan OpenArray Human miRNA Panels. Principal component analysis indicated differences in male versus female miRNA profiles. The miRNA array analysis revealed two miRNAs which were significantly increased in the female samples (miR-885-5p; fold change (FC):5.07, adjusted p value: 0.026 and miR-193a-5p; FC:2.6, adjusted p value: 0.031), although only miR-885-5p was validated as increased in females using specific qPCR assay (p < 0.0001). Gene ontology analysis of miR-885-5p validated targets identified cell migration, motility and fibrosis as processes potentially affected, with RAC1-mediated signalling featuring significantly. There is a significant increase in miR-885-5p in plasma of females versus males with CF under six years of age. Cystic fibrosis (CF) is an autosomal recessive genetic disorder arising from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene 1. CFTR is a crucial chloride ion channel expressed by epithelial cells in the lung and other organs. The consequences of defective CFTR are most severely manifested in the lung, where the imbalanced ion homeostasis results in chronic airway inflammation, which leads to a progressive and ultimately fatal decline in lung function. Despite improved therapies and increased life expectancy for both males and females with CF in recent years, a gender dichotomy persists whereby females are at a clinical disadvantage e.g. poorer lung function, earlier colonisation by chronic mucoid Pseudomonas aeruginosa, greater frequency of exacerbations, and lower median survival age 2-7. Whether sex differences exist in children with CF remains controversial 8,9. The ability to measure and monitor lung disease in children via a non-invasive method would be highly beneficial for CF clinical care. Molecular biomarkers that are prognostic for lung disease progression could serve, in support of clinical examination, to allow earlier and hence more effective intervention strategies. Ideally these would be molecules that are stable in body fluids (e.g. plasma), able to be quantified with reliance and accuracy, and mechanistically linked to pulmonary infection and/or inflammation. MicroRNAs are small non-coding RNAs that bind specific target mRNA sequences to inhibit their expression. As well as being expressed within cells/tissues, miRNAs are also present extracellularly, and are readily detectable in body fluids such as serum and plasma. In contrast to mRNA, miRNAs circulating in plasma are surprisingly resistant to RNase degradation due to the fact they are found either packaged inside microvesicles e.g. exosomes, or associated with protein/lipid complexes e.g. argonaute 2 or high density lipoprotein 10. Although the role of circulating miRNAs is not...

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Non-coding RNA in cystic fibrosis

Cited by 35 publications

References 91 publications

Alpha-1 Antitrypsin—A Target for MicroRNA-Based Therapeutic Development for Cystic Fibrosis

Alpha-1 Antitrypsin—A Target for MicroRNA-Based Therapeutic Development for Cystic Fibrosis

Potential Regulatory Roles of MicroRNAs and Long Noncoding RNAs in Anticancer Therapies

Plasma microRNA levels in male and female children with cystic fibrosis

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