miR-320c Regulates SERPINA1 Expression and Is Induced in Patients With Pulmonary Disease
Arch Bronconeumol (Engl Ed). 2020 May 18:S0300-2896(20)30084-3.
doi: 10.1016/j.arbres.2020.03.006.
Online ahead of print.
[Article in
English,
Spanish]
Authors
Nerea Matamala
1
, Beatriz Lara
2
, Gema Gómez-Mariano
1
, Selene Martínez
1
, Irene Vázquez-Domínguez
3
, Álvaro Otero-Sobrino
1
, Antonio Muñoz-Callejas
1
, Elena Sánchez
1
, Cristina Esquinas
4
, Ana Bustamante
5
, Sergio Cadenas
6
, Sergio Curi
7
, Lourdes Lázaro
8
, María Teresa Martínez
9
, Esther Rodríguez
10
, Marc Miravitlles
10
, María Torres-Duran
11
, Inés Herrero
12
, Francisco Javier Michel
13
, Silvia Castillo
14
, José Mª Hernández-Pérez
15
, Ignacio Blanco
16
, Francisco Casas
17
, Beatriz Martínez-Delgado
18
Affiliations
- 1 Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), CIBER de Enfermedades Raras (CIBERER), Madrid, Spain.
- 2 Respiratory Medicine Department, Coventry University Hospital, Coventry, UK.
- 3 Centro de Biología Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain.
- 4 Registro Español de pacientes con déficit de alfa-1 antitripsina (REDAAT), Fundación Española de Pulmón, Respira, SEPAR, Barcelona, Spain; Servicio de Neumología, Hospital Universitari Vall d'Hebron/Vall d'Hebron Institut de Recerca (VHIR), CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
- 5 Servicio de Neumología, Hospital de Sierrallana, Torrelavega, Cantabria, Spain.
- 6 Servicio de Neumología, Hospital Clínico Universitario de Salamanca, Spain.
- 7 Complejo Hospitalario de Navarra, Pamplona, Spain.
- 8 Servicio de Neumología, Complejo Asistencial Universitario de Burgos, Spain.
- 9 Servicio de Neumología, Hospital Universitario Doce de Octubre, Madrid, Spain.
- 10 Servicio de Neumología, Hospital Universitari Vall d'Hebron/Vall d'Hebron Institut de Recerca (VHIR), CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
- 11 Servicio de Neumología, Hospital Álvaro Cunqueiro, EOXI Vigo, Pneumovigo I+i, IIS Galicia Sur, Spain.
- 12 Hospital Universitario Miguel Servet, Zaragoza, Spain.
- 13 Servicio de Neumología, Hospital Universitario Donostia, País Vasco, Spain.
- 14 Unidad de Neumología infantil y Fibrosis quística, Hospital Clínico Universitario de Valencia, Spain.
- 15 Servicio de Neumología, Hospital General de la Palma, Canarias, Spain.
- 16 Registro Español de pacientes con déficit de alfa-1 antitripsina (REDAAT), Fundación Española de Pulmón, Respira, SEPAR, Barcelona, Spain.
- 17 Servicio de Neumología, Hospital Universitario San Cecilio, Granada, Spain.
- 18 Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), CIBER de Enfermedades Raras (CIBERER), Madrid, Spain. Electronic address: bmartinezd@isciii.es.
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 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 miR-320. 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 pro-inflammatory 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.
Keywords:
Alpha-1 antitrypsin deficiency; Déficit de alfa-1 antitripsina; Enfermedad pulmonar; Inflamación; Inflammation; Lung disease; miR-320c; microARNs; microRNA.
Copyright © 2020 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.