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miR-320c Regulates SERPINA1 expression and is induced in patients with pulmonary disease

Abstract: Introduction Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3?UTR region of Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3 UTR region of SERPINA1 gene. In this study we explore the involvement of miR-320c, a member of this family, in this disease. Methods: Firstly in vitro studies were carried out to demonstrate regulation of SERPINA1 gene by miR320. Furthermore, the expression of miR-320c was analyzed in the blood of 98 individuals with different AAT serum levels by using quantitative PCR and expression was correlated to clinical parameters of the patients. Finally, HL60 cells were used to analyze induction of miR-320c in inflammatory conditions. Results: Overexpression of miR-320 members in human HepG2 cells led to inhibition of SERPINA1 expression. Analysis of miR-320c expression in patient?s samples revealed significantly increased expression of miR-320c in individuals with pulmonary disease. Additionally, HL60 cells treated with the proinflammatory factor lipopolysaccharide (LPS) showed increase in miR-320c expression, suggesting that miR-320c responds to inflammation. Conclusion: Our findings demonstrate that miR-320c inhibits SERPINA1 expression in a hepatic cell line and its levels in blood are associated with lung disease in a cohort of patients with different AAT serum levels. These results suggest that miR-320c can play a role in AAT regulation and could be a biomarker of inflammatory processes in pulmonary diseases.

 Fuente: Archivos de Bronconeumología, 2021, 57(7), 457-463

 Editorial: Elsevier Doyma

 Año de publicación: 2021

 Nº de páginas: 7

 Tipo de publicación: Artículo de Revista

 DOI: 10.1016/j.arbr.2020.03.031

 ISSN: 0300-2896,1579-2129,2173-5751

 Url de la publicación: https://doi.org/10.1016/j.arbr.2020.03.031

Autoría

MATAMALA, NEREA

LARA, BEATRIZ

GÓMEZ-MARIANO, GEMA

MARTÍNEZ, SELENE

VÁZQUEZ-DOMÍNGUEZ, IRENE

OTERO-SOBRINO, ÁLVARO

MUÑOZ-CALLEJAS, ANTONIO

SÁNCHEZ, ELENA

ESQUINAS, CRISTINA

ANA JOSE BUSTAMANTE RUIZ

CADENAS, SERGIO

CURI, SERGIO

LÁZARO, LOURDES

MARTÍNEZ, MARÍA TERESA

RODRÍGUEZ, ESTHER

MIRAVITLLES, MARC

TORRES-DURÁN, MARÍA

HERRERO, INÉS

MICHEL, FRANCISCO JAVIER

CASTILLO, SILVIA