Rebeca Martínez-Hernández1, Miguel Sampedro-Núñez1, Ana Serrano-Somavilla1, Ana M Ramos-Leví1, Hortensia de la Fuente2,3, Juan Carlos Triviño4, Ancor Sanz-García5, Francisco Sánchez-Madrid2,3, Mónica Marazuela1. 1. Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain. 2. Department of Immunology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Universidad Autónoma de Madrid, Madrid, Spain. 3. CIBER de Enfermedades Cardiovasculares (CIBERCV) and Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. 4. Sistemas Genómicos, Valencia, Spain. 5. Neurosurgery & National Reference Unit for the Treatment of Refractory Epilepsy, Instituto de Investigación Sanitaria Hospital de la Princesa, Madrid, Spain.
Abstract
Context: Circulating microRNAs (miRNAs) are emerging as an interesting research area because of their potential role as novel biomarkers and therapeutic targets. Their involvement in autoimmune thyroid diseases (AITDs) has not been fully explored. Objective: To compare the expression profile of miRNAs in thyroid tissue from patients with AITD and controls, using next-generation sequencing, further validated our findings in thyroid and serum samples. Design: Twenty fresh-frozen thyroid tissues (15 from patients with AITD and 5 from controls) were used for miRNA next-generation sequencing. Thirty-six thyroid samples were recruited for the qRT-PCR validation test and 58 serum samples for further validation in peripheral blood. Results: Expression of several miRNAs that had been previously associated with relevant immunological functions was significantly dysregulated. Specifically, eight differentially expressed miRNAs (miR-21-5p, miR-142-3p, miR-146a-5p, miR-146b-5p, miR-155-5p, miR-338-5p, miR-342-5p, and miR-766-3p) were confirmed using qRT-PCR in thyroid samples, and three had the same behavior in tissue and serum samples (miR-21-5p, miR-142-3p, and miR-146a-5p). Furthermore, when the expression of these miRNAs was assessed together with five additional ones previously related to AITD in peripheral blood, the expression of five (miR-Let7d-5p, miR-21-5p, miR-96-5p, miR-142-3p, and miR-301a-3p) was significantly expressed in AITD and, in patients with Graves disease (GD), was correlated with a higher severity of disease, including active ophthalmopathy, goiter, higher antibody titers, and/or higher recurrence rates. Conclusions: The present findings identify a serum five-signature miRNA that could be an independent risk factor for developing AITD and a predisposition of a worse clinical picture in patients with GD.
Context: Circulating microRNAs (miRNAs) are emerging as an interesting research area because of their potential role as novel biomarkers and therapeutic targets. Their involvement in autoimmune thyroid diseases (AITDs) has not been fully explored. Objective: To compare the expression profile of miRNAs in thyroid tissue from patients with AITD and controls, using next-generation sequencing, further validated our findings in thyroid and serum samples. Design: Twenty fresh-frozen thyroid tissues (15 from patients with AITD and 5 from controls) were used for miRNA next-generation sequencing. Thirty-six thyroid samples were recruited for the qRT-PCR validation test and 58 serum samples for further validation in peripheral blood. Results: Expression of several miRNAs that had been previously associated with relevant immunological functions was significantly dysregulated. Specifically, eight differentially expressed miRNAs (miR-21-5p, miR-142-3p, miR-146a-5p, miR-146b-5p, miR-155-5p, miR-338-5p, miR-342-5p, and miR-766-3p) were confirmed using qRT-PCR in thyroid samples, and three had the same behavior in tissue and serum samples (miR-21-5p, miR-142-3p, and miR-146a-5p). Furthermore, when the expression of these miRNAs was assessed together with five additional ones previously related to AITD in peripheral blood, the expression of five (miR-Let7d-5p, miR-21-5p, miR-96-5p, miR-142-3p, and miR-301a-3p) was significantly expressed in AITD and, in patients with Graves disease (GD), was correlated with a higher severity of disease, including active ophthalmopathy, goiter, higher antibody titers, and/or higher recurrence rates. Conclusions: The present findings identify a serum five-signature miRNA that could be an independent risk factor for developing AITD and a predisposition of a worse clinical picture in patients with GD.
Authors: Rebeca Martínez-Hernández; Ana Serrano-Somavilla; Ana Ramos-Leví; Miguel Sampedro-Nuñez; Alberto Lens-Pardo; José Luis Muñoz De Nova; Juan Carlos Triviño; María Ujue González; Lorena Torné; Javier Casares-Arias; Noa B Martín-Cófreces; Francisco Sánchez-Madrid; Mónica Marazuela Journal: EBioMedicine Date: 2019-11-14 Impact factor: 8.143
Authors: Letizia Pitto; Francesca Gorini; Fabrizio Bianchi; Elena Guzzolino Journal: Int J Environ Res Public Health Date: 2020-10-24 Impact factor: 3.390