Gender-related differences in expression of microRNAs in cystic fibrosis

Informations projet

GENDER-CF

N° de convention de subvention: 707771

DOI

10.3030/707771

Projet clôturé

Date de signature de la CE 11 Mars 2016

Date de début 1 Septembre 2017

Date de fin 31 Août 2019

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 175 866,00

Contribution de l’UE

€ 175 866,00

Coordonné par

ROYAL COLLEGE OF SURGEONS IN IRELAND
Ireland

Periodic Reporting for period 1 - GENDER-CF (Gender-related differences in expression of microRNAs in cystic fibrosis)

Période du rapport: 2017-09-01 au 2019-08-31

Résumé du contexte et des objectifs généraux du projet

Cystic fibrosis (CF) is a life-limiting genetic disorder that causes progressive damage to the lungs. It is the most common lethal hereditary disorder in the Caucasian population. Gender differences persist within the CF community whereby females are at a clinical disadvantage, showing poorer lung function and lower survival age. The overall objective of this research project is to find new mechanisms for the differences between males and females with cystic fibrosis lung disease, as this knowledge could be used to develop new therapies to benefit all patients.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

MicroRNAs are short nucleotide sequences that regulate expression of specific target genes, and can be found in bodily fluids such as plasma. We compared the expression profile of hundreds of miRNAs in plasma samples from male and female children with CF and analysed these expression profiles for correlations with various parameters such as CFTR genotype, age, lung infection status and antibiotic treatment. We found that miR-885-5p levels were significantly increased in the female samples. We then performed bioinformatic gene ontology and pathway analysis of miR-885-5p validated target genes in order to gain insight into the possible biological significance of miR-885-5p within the context of CF progression. RAC1-mediated signaling was the most dominant result from these analyses which may have wide-ranging implications in CF, including its role in enhancing the rescue of cystic fibrosis transmembrane conductance regulator (CFTR) to the cell surface membrane in concert with pharmacological correctors. Other pathways of relevance include cell migration/motility, inflammation and fibrosis.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

We report an important finding of a novel miRNA which differentiates between male and female pediatric CF plasma samples and may contribute to aggravated CF pathogenesis in females with the disease. Mechanistic studies are warranted in the future in order to test if increased levels of miR-885-5p in female CF plasma are representative of a functional difference, and therefore potentially useful as a clinical biomarker for monitoring CF disease progression or response to CFTR modulator treatment.

msca-cover-figure.jpg