scholarly journals A Peptide-Nucleic Acid Targeting miR-335-5p Enhances Expression of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene with the Possible Involvement of the CFTR Scaffolding Protein NHERF1

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 117
Author(s):  
Anna Tamanini ◽  
Enrica Fabbri ◽  
Tiziana Jakova ◽  
Jessica Gasparello ◽  
Alex Manicardi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Nucleic Acid ◽  
Peptide Nucleic Acid ◽  
Stop Codon ◽  
Scaffolding Protein ◽  
Cftr Gene ◽  
Scaffolding Proteins ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane

(1) Background: Up-regulation of the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) might be of great relevance for the development of therapeutic protocols for cystic fibrosis (CF). MicroRNAs are deeply involved in the regulation of CFTR and scaffolding proteins (such as NHERF1, NHERF2 and Ezrin). (2) Methods: Content of miRNAs and mRNAs was analyzed by RT-qPCR, while the CFTR and NHERF1 production was analyzed by Western blotting. (3) Results: The results here described show that the CFTR scaffolding protein NHERF1 can be up-regulated in bronchial epithelial Calu-3 cells by a peptide-nucleic acid (PNA) targeting miR-335-5p, predicted to bind to the 3′-UTR sequence of the NHERF1 mRNA. Treatment of Calu-3 cells with this PNA (R8-PNA-a335) causes also up-regulation of CFTR. (4) Conclusions: We propose miR-335-5p targeting as a strategy to increase CFTR. While the efficiency of PNA-based targeting of miR-335-5p should be verified as a therapeutic strategy in CF caused by stop-codon mutation of the CFTR gene, this approach might give appreciable results in CF cells carrying other mutations impairing the processing or stability of CFTR protein, supporting its application in personalized therapy for precision medicine.

scholarly journals A Novel Cystic Fibrosis Gene Mutation C.4242+1G>C in an Omani Patient: A Case Report

2021 ◽  
Vol 36 (2) ◽  
pp. e243-e243
Author(s):  
Said Al Balushi ◽  
Younis Al Balushi ◽  
Moza Al Busaidi ◽  
Latifa Al Mutawa
Keyword(s):  
Cystic Fibrosis ◽  
Gene Mutation ◽  
Digestive System ◽  
The Body ◽  
Cystic Fibrosis Gene ◽  
Cftr Gene ◽  
Sweat Test ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis (CF) is a genetic disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that affects multisystems in the body, particularly the lungs and digestive system. We report a case of an Omani newborn who presented with meconium ileus and high suspicion of CF. Thus, full CFTR gene sequencing was performed, which revealed a homozygous unreported C.4242+1G>C novel gene mutation. Both parents were found to be heterozygous for this mutation. This case sheds light on the importance of the extensive genetic testing of typical CF cases in the absence of family history or during neonatal presentations, especially when the sweat test cannot be performed and the diagnosis can be challenging.

scholarly journals 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

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1677 ◽  
Author(s):  
Shaiq Sultan ◽  
Andrea Rozzi ◽  
Jessica Gasparello ◽  
Alex Manicardi ◽  
Roberto Corradini ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Binding Site ◽  
Peptide Nucleic Acid ◽  
Therapeutic Strategy ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Treatment Protocols ◽  
Cftr Protein ◽  
Cystic Fibrosis Transmembrane ◽  
Different Levels

Peptide nucleic acids (PNAs) have been demonstrated to be very useful tools for gene regulation at different levels and with different mechanisms of action. In the last few years the use of PNAs for targeting microRNAs (anti-miRNA PNAs) has provided impressive advancements. In particular, targeting of microRNAs involved in the repression of the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is defective in cystic fibrosis (CF), is a key step in the development of new types of treatment protocols. In addition to the anti-miRNA therapeutic strategy, inhibition of miRNA functions can be reached by masking the miRNA binding sites present within the 3′UTR region of the target mRNAs. The objective of this study was to design a PNA masking the binding site of the microRNA miR-145-5p present within the 3′UTR of the CFTR mRNA and to determine its activity in inhibiting miR-145-5p function, with particular focus on the expression of both CFTR mRNA and CFTR protein in Calu-3 cells. The results obtained support the concept that the PNA masking the miR-145-5p binding site of the CFTR mRNA is able to interfere with miR-145-5p biological functions, leading to both an increase of CFTR mRNA and CFTR protein content.

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