Developmental control of <i>CFTR</i>: from bioinformatics to novel therapeutic approaches

Greene, Catherine M.; Hartl, Dominik

doi:10.1183/09031936.00138914

Cited by 3 publications

(3 citation statements)

References 18 publications

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“…This finding was confirmed by another research group in CF tissues [50]. This is relevant, considering the increasing interest in RNA-targeting therapies for CF [51][52][53][54][55].…”

Section: Introductionsupporting

confidence: 74%

Treatment of human airway epithelial Calu-3 cells with a peptide-nucleic acid (PNA) targeting the microRNA miR-101-3p is associated with increased expression of the cystic fibrosis Transmembrane Conductance Regulator () gene

Fabbri

Tamanini

Jakova

et al. 2021

European Journal of Medicinal Chemistry

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“…This finding was confirmed by another research group in CF tissues [50]. This is relevant, considering the increasing interest in RNA-targeting therapies for CF [51][52][53][54][55].…”

Section: Introductionsupporting

confidence: 74%

Treatment of human airway epithelial Calu-3 cells with a peptide-nucleic acid (PNA) targeting the microRNA miR-101-3p is associated with increased expression of the cystic fibrosis Transmembrane Conductance Regulator () gene

Fabbri

Tamanini

Jakova

et al. 2021

European Journal of Medicinal Chemistry

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“…In a recent paper, we demonstrated that the activity of miR-509-3p miRNA, one of the miRNAs involved in the post-transcriptional regulation of the CFTR gene, could be inhibited using 14 or 7 bases long PNAs [ 14 , 15 ]. However, this type of strategy, as evidenced by some authors [ 26 , 39 ], has enormous off-target effects, because every miRNA regulates hundreds or thousands of mRNA targets. Alternatively, the use of miRNA Target Protectors (TPs) has been proposed as a promising option for the development of effective tools for the correction of CFTR expression in people with CF.…”

Section: Discussionmentioning

confidence: 99%

Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis

et al. 2017

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Cystic Fibrosis (CF) is one of the most common life shortening conditions in Caucasians. CF is caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene which result in reduced or altered CFTR functionality. Several microRNAs (miRNAs) downregulate the expression of CFTR, thus causing or exacerbating the symptoms of CF. In this context, the design of anti-miRNA agents represents a valid functional tool, but its translation to the clinic might lead to unpredictable side effects because of the interference with the expression of other genes regulated by the same miRNAs. Herein, for the first time, is proposed the use of peptide nucleic acids (PNAs) to protect specific sequences in the 3’UTR (untranslated region) of the CFTR messenger RNA (mRNA) by action of miRNAs. Two PNAs (7 and 13 bases long) carrying the tetrapeptide Gly-SerP-SerP-Gly at their C-end, fully complementary to the 3’UTR sequence recognized by miR-509-3p, have been synthesized and the structural features of target PNA/RNA heteroduplexes have been investigated by spectroscopic and molecular dynamics studies. The co-transfection of the pLuc-CFTR-3´UTR vector with different combinations of PNAs, miR-509-3p, and controls in A549 cells demonstrated the ability of the longer PNA to rescue the luciferase activity by up to 70% of the control, thus supporting the use of suitable PNAs to counteract the reduction in the CFTR expression.

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“…Having compared the miRNA expression profiles of adult and foetal lungs, three miRNAs in particular (miR-145, miR-150, and miR-451) were found to have a temporal effect, being significantly upregulated in the adult lung and therefore contributing to downregulation of CFTR. They also demonstrated how inhibitors based on these miRNAs can affect CFTR gene expression and function in air-liquid interface culture and suggest that these may be developed as tools for CFTR correction in people with CF [ 76 ].…”

Section: Micrornamentioning

confidence: 99%

MicroRNA Dysregulation in Cystic Fibrosis

McKiernan

Greene

2015

Mediators of Inflammation

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The cystic fibrosis lung is a complex milieu comprising multiple factors that coordinate its physiology. MicroRNAs are regulatory factors involved in most biological processes and it is becoming increasingly clear that they play a key role in the development and manifestations of CF lung disease. These small noncoding RNAs act posttranscriptionally to inhibit protein production. Their involvement in the pathogenesis of CF lung disease stems from the fact that their expression is altered in vivo in the CF lung due to intrinsic and extrinsic factors; to date defective chloride ion conductance, endoplasmic reticulum stress, inflammation, and infection have been implicated in altering endogenous miRNA expression in this setting. Here, the current state-of-the-art and biological consequences of altered microRNA expression in cystic fibrosis are reviewed.

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Developmental control of CFTR: from bioinformatics to novel therapeutic approaches

Cited by 3 publications

References 18 publications

Treatment of human airway epithelial Calu-3 cells with a peptide-nucleic acid (PNA) targeting the microRNA miR-101-3p is associated with increased expression of the cystic fibrosis Transmembrane Conductance Regulator () gene

Treatment of human airway epithelial Calu-3 cells with a peptide-nucleic acid (PNA) targeting the microRNA miR-101-3p is associated with increased expression of the cystic fibrosis Transmembrane Conductance Regulator () gene

Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis

MicroRNA Dysregulation in Cystic Fibrosis

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