Gender-related differences in expression of microRNAs in cystic fibrosis

Información del proyecto

GENDER-CF

Identificador del acuerdo de subvención: 707771

DOI

10.3030/707771

Proyecto cerrado

Fecha de la firma de la CE 11 Marzo 2016

Fecha de inicio 1 Septiembre 2017

Fecha de finalización 31 Agosto 2019

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 175 866,00

Aportación de la UE

€ 175 866,00

Coordinado por

ROYAL COLLEGE OF SURGEONS IN IRELAND
Ireland

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

Período documentado: 2017-09-01 hasta 2019-08-31

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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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