A Peptide Nucleic Acid (PNA) Masking the miR-145-5p Binding Site of the 3′UTR of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mRNA Enhances CFTR Expression in Calu-3 Cells

Sultan, Shaiq; Rozzi, Andrea; Gasparello, Jessica; Manicardi, Alex; Corradini, Roberto; Papi, Chiara; Finotti, Alessia; Reali, Eva; Cabrini, Giulio; Gambari, Roberto; Borgatti, Monica

doi:10.3390/molecules25071677

Cited by 20 publications

(15 citation statements)

References 51 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…targeting the binding site of miR‐145‐5p within the 3′UTR of the CFTR mRNA in Calu‐3 cells, showing that PNA masking was able to interfere with the miR‐145‐5p activity, leading to the increase in both CFTR mRNA and protein levels. [ 39 ] Despite the promising nature of these results that clearly illustrates the possibility of using anti‐miR PNA as a therapeutic modality for CF, the in vitro data showcased in these studies presents only a proof‐of‐principle and further experimentation is need to evaluate their in vivo application potential.…”

Section: Pna In Regulating Gene Expressionmentioning

confidence: 99%

Peptide nucleic acids and their role in gene regulation and editing

2021

View full text Add to dashboard Cite

The unique properties of peptide nucleic acid (PNA) makes it a desirable candidate to be used in therapeutic and biotechnological interventions. It has been broadly utilized for numerous applications, with a major focus in regulation of gene expression, and more recently in gene editing. While the classic PNA design has mainly been employed to date, chemical modifications of the PNA backbone and nucleobases provide an avenue to advance the technology further. This review aims to discuss the recent developments in PNA based gene manipulation techniques and the use of novel chemical modifications to improve the current state of PNA mediated gene targeting.

show abstract

Section: Pna In Regulating Gene Expressionmentioning

confidence: 99%

Peptide nucleic acids and their role in gene regulation and editing

2021

View full text Add to dashboard Cite

show abstract

“…PNAs may be used to target specific miRNAs that are involved in the regulation of the expression of the CFTR gene [ 119 , 120 ]. For instance, PNAs designed to target miR-145, miR-509-3p, and miR-101-3p restored the expression of CFTR in vitro [ 61 , 121 , 122 , 123 ]. Additionally, PNAs can also be used as miRNA target protectors.…”

Section: Therapeutic Modulation Of Micrornas In Cystic Fibrosismentioning

confidence: 99%

The Multifaceted Roles of MicroRNAs in Cystic Fibrosis

et al. 2020

View full text Add to dashboard Cite

Cystic fibrosis (CF) is a lifelong disorder affecting 1 in 3500 live births worldwide. It is a monogenetic autosomal recessive disease caused by loss-of-function mutations in the gene encoding the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR), the impairment of which leads to ionic disequilibria in exocrine organs. This translates into a chronic multisystemic disease characterized by airway obstruction, respiratory infections, and pancreatic insufficiency as well as hepatobiliary and gastrointestinal dysfunction. Molecular characterization of the mutational heterogeneity of CFTR (affected by more than 2000 variants) improved the understanding and management of CF. However, these CFTR variants are linked to different clinical manifestations and phenotypes, and they affect response to treatments. Expanding evidence suggests that multisystemic disease affects CF pathology via impairing either CFTR or proteins regulated by CFTR. Thus, altering the expression of miRNAs in vivo could constitute an appealing strategy for developing new CF therapies. In this review, we will first describe the pathophysiology and clinical management of CF. Then, we will summarize the current knowledge on altered miRNAs in CF patients, with a focus on the miRNAs involved in the deregulation of CFTR and in the modulation of inflammation. We will highlight recent findings on the potential utility of measuring circulating miRNAs in CF as diagnostic, prognostic, and predictive biomarkers. Finally, we will provide an overview on potential miRNA-based therapeutic approaches.

show abstract

“…Consistently, suppression of miR-145 has been shown to restore F508del CFTR expression ( Lutful Kabir et al, 2018 ; Dutta et al, 2019 ). Further, a recent study shows PNA masking of the miR-145-5p binding site of CFTR mRNA upregulates CFTR at both mRNA and protein levels ( Sultan et al, 2020 ). Similar PNA targeting of miR-101-3p also upregulates CFTR ( Fabbri et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Role of Non-Coding RNAs in Post-Transcriptional Regulation of Lung Diseases

Soni

Biswas

2021

Front. Genet.

View full text Add to dashboard Cite

Non-coding RNAs (ncRNAs), notably microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have recently gained increasing consideration because of their versatile role as key regulators of gene expression. They adopt diverse mechanisms to regulate transcription and translation, and thereby, the function of the protein, which is associated with several major biological processes. For example, proliferation, differentiation, apoptosis, and metabolic pathways demand fine-tuning for the precise development of a specific tissue or organ. The deregulation of ncRNA expression is concomitant with multiple diseases, including lung diseases. This review highlights recent advances in the post-transcriptional regulation of miRNAs and lncRNAs in lung diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis. Further, we also discuss the emerging role of ncRNAs as biomarkers as well as therapeutic targets for lung diseases. However, more investigations are required to explore miRNAs and lncRNAs interaction, and their function in the regulation of mRNA expression. Understanding these mechanisms might lead to early diagnosis and the development of novel therapeutics for lung diseases.

show abstract

A Peptide Nucleic Acid (PNA) Masking the miR-145-5p Binding Site of the 3′UTR of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mRNA Enhances CFTR Expression in Calu-3 Cells

Cited by 20 publications

References 51 publications

Peptide nucleic acids and their role in gene regulation and editing

Peptide nucleic acids and their role in gene regulation and editing

The Multifaceted Roles of MicroRNAs in Cystic Fibrosis

Role of Non-Coding RNAs in Post-Transcriptional Regulation of Lung Diseases

Contact Info

Product

Resources

About