Exploitation of a Very Small Peptide Nucleic Acid as a New Inhibitor of miR-509-3p Involved in the Regulation of Cystic Fibrosis Disease-Gene Expression

Amato, Felice; Tomaiuolo, Rossella; Nici, Fabrizia; Borbone, Nicola; Elce, Ausilia; Catalanotti, Bruno; D’Errico, Stefano; Morgillo, Carmine Marco; Rosa, Giuseppe De; Mayol, Laura; Piccialli, Gennaro; Oliviero, Giorgia; Castaldo, Giuseppe

doi:10.1155/2014/610718

Cited by 47 publications

(49 citation statements)

References 48 publications

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“…This report adds significantly to our existing knowledge regarding miRNA regulation of CFTR [5- 10,13] and the developing field of miR-based CFTR therapeutics [15]. The data confirms previous studies implicating miR-145 and miR-101 as important modulators of CFTR expression [5,6,8,9] and build on them by demonstrating how MBBOs based on these miRNAs can affect CFTR gene expression and CFTR protein function.…”

supporting

confidence: 84%

Developmental control of CFTR: from bioinformatics to novel therapeutic approaches

Greene

Hartl

2014

Eur Respir J

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supporting

confidence: 84%

Developmental control of CFTR: from bioinformatics to novel therapeutic approaches

Greene

Hartl

2014

Eur Respir J

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“…Numerous miRNAs had altered expression between CF and non-CF bronchial epithelium, and some of the altered miRNAs were predicted to regulate CFTR. Various other published studies have examined the role of miRNAs in the direct or indirect control of wild type (wt) or mutant CFTR expression [41][42][43][45][46][47][48][49][50].…”

Section: Other Mechanisms Affecting Cftr Expression In Cfmentioning

confidence: 99%

CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease

Fernández

Santi

Rose

et al. 2018

Expert Review of Respiratory Medicine

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Obstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are causes of high morbidity and mortality worldwide. CF is a multiorgan genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is characterized by progressive chronic obstructive lung disease. Most cases of COPD are a result of noxious particles, mainly cigarette smoke but also other environmental pollutants. Areas covered: Although the pathogenesis and pathophysiology of CF and COPD differ, they do share key phenotypic features and because of these similarities there is great interest in exploring common mechanisms and/or factors affected by CFTR mutations and environmental insults involved in COPD. Various molecular, cellular and clinical studies have confirmed that CFTR protein dysfunction is common in both the CF and COPD airways. This review provides an update of our understanding of the role of dysfunctional CFTR in both respiratory diseases. Expert commentary: Drugs developed for people with CF to improve mutant CFTR function and enhance CFTR ion channel activity might also be beneficial in patients with COPD. A move toward personalized therapy using, for example, microRNA modulators in conjunction with CFTR potentiators or correctors, could enhance treatment of both diseases.

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“…[8][9][10][11][12][13] The range of applications of nucleopeptides recalls that of peptide nucleic acids (PNAs), the known DNA analogs, which are achiral, non-charged oligomers with a pseudo-peptide backbone, largely used in numerous diagnostic, antigene, and antisense strategies. [14][15][16][17][18][19][20] sequence with unmodified l-Dap, affording a cationic oligomer as a result of the protonation of the side chain amino groups at physiological pH. Thus, in addition to favorable H-bonding, potential electrostatic interactions are originated between oligoDapT and nucleic acids ( Figure S2).…”

Section: Introductionmentioning

confidence: 99%

DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications

Musumeci

Roviello

2018

IJN

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BackgroundNucleobase-bearing peptides and their interaction with DNA and RNA are an important topic in the development of therapeutic approaches. On one hand, they are highly effective for modulating the nucleic-acid-based biological processes. On the other hand, they permit to overcome some of the main factors limiting the therapeutic efficacy of natural oligonucleotides, such as their rapid degradation by nucleases.Methods and resultsThis article describes the synthesis and characterization of a novel thymine-bearing nucleoamino acid based on the l-diaminopropionic acid (l-Dap) and its solid phase oligomerization to α-peptides (oligoDapT), characterized using mass spectrometry, spectroscopic techniques, and scanning electron microscopy (SEM) analysis. The interaction of the obtained nucleopeptide with DNA and RNA model systems as both single strands (dA12, rA12, and poly(rA)) and duplex structures (dA12/dT12 and poly(rA)/poly(rU)) was investigated by means of circular dichroism (CD) and ultraviolet (UV) experiments. From the analysis of our data, a clear ability of the nucleopeptide to bind nucleic acids emerged, with oligoDapT being able to form stable complexes with both unpaired and double-stranded DNA and RNA. In particular, dramatic changes in the dA12/dT12 and poly(rA)/poly(rU) structures were observed as a consequence of the nucleopeptide binding. CD titrations revealed that multiple peptide units bound all the examined nucleic acid targets, with TLdap/A or TLdap/A:T(U) ratios >4 in case of oligoDapT/DNA and ~2 in oligoDapT/RNA complexes.ConclusionOur findings seem to indicate that Dap-based nucleopeptides are interesting nucleic acid binding-tools to be further explored with the aim to efficiently modulate DNA- and RNA-based biological processes.

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Exploitation of a Very Small Peptide Nucleic Acid as a New Inhibitor of miR-509-3p Involved in the Regulation of Cystic Fibrosis Disease-Gene Expression

Cited by 47 publications

References 48 publications

Developmental control of CFTR: from bioinformatics to novel therapeutic approaches

Developmental control of CFTR: from bioinformatics to novel therapeutic approaches

CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease

DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications

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