Gender-related differences in expression of microRNAs in cystic fibrosis

Informazioni relative al progetto

GENDER-CF

ID dell’accordo di sovvenzione: 707771

DOI

10.3030/707771

Progetto chiuso

Data della firma CE 11 Marzo 2016

Data di avvio 1 Settembre 2017

Data di completamento 31 Agosto 2019

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 175 866,00

Contributo UE

€ 175 866,00

Coordinato da

ROYAL COLLEGE OF SURGEONS IN IRELAND
Ireland

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

Periodo di rendicontazione: 2017-09-01 al 2019-08-31

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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.

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