Analysis of miRNA expression in patients with rheumatoid arthritis during remission and relapse after a 5-year trial of tofacitinib treatment.

Autor: Fernández-Ruiz JC; Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, Mexico; Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico., Ramos-Remus C; Universidad Autónoma de Guadalajara, Jalisco, Mexico., Sánchez-Corona J; División de Medicina Molecular del Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico., Castillo-Ortiz JD; Unidad de Investigación en Enfermedades Crónico-Degenerativas, Guadalajara, Jalisco, Mexico., Castañeda-Sánchez JJ; Unidad de Investigación en Enfermedades Crónico-Degenerativas, Guadalajara, Jalisco, Mexico., Bastian Y; Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, Mexico; Cátedras CONACYT, Consejo Nacional de Ciencia y Tecnología, Mexico., Romo-García MF; Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, Mexico; Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico., Ochoa-González F; Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, Mexico., Monsivais-Urenda AE; Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico., González-Amaro R; Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico., Enciso-Moreno JA; Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, Mexico., Castañeda-Delgado JE; Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, Mexico; Cátedras CONACYT, Consejo Nacional de Ciencia y Tecnología, Mexico. Electronic address: jecastanedade@conacyt.mx.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2018 Oct; Vol. 63, pp. 35-42. Date of Electronic Publication: 2018 Jul 31.
DOI: 10.1016/j.intimp.2018.07.028
Abstrakt: The physiopathology of rheumatoid arthritis (RA) is mediated by proinflammatory cytokines, some of which are regulated by the JAK/STAT pathway. Tofacitinib is a JAK inhibitor, but its role in the regulation of microRNAs (miRNAs) is unknown. There is also no information regarding the role of miRNAs in the clinical relapse/remission of RA. The present project aims to identify a signature profile of miRNA expression in a subgroup of RA patients who had to discontinue tofacitinib treatment (because of the ending of a 5-year open-label clinical trial) and to describe the expression of miRNAs during RA remission or flare-up. The relative expression of 61 miRNAs was determined in serum samples with the Firefly™ BioWorks assay. Statistical analysis was performed by means of Student's t-test and heatmap analysis was performed with Firefly™ Analysis Workbench software and in the software GraphPad® Prism v5.0. Target prediction and Gene Ontology analysis were carried out using bioinformatic tools. We found a distinctive signature of miRNA expression associated with relapse, featuring upregulated expression of hsa‑miR‑432‑5p (p < 0.05). We also found upregulation of hsa‑miR‑194‑5p (p < 0.05) in samples of patients with RA flare-up. Gene Ontology analysis of the target genes for hsa‑miR‑432‑5p was performed to identify relevant pathways associated with relapse; the implications of these pathways in the physiopathology of RA are discussed. Tofacitinib treatment does not have a direct effect on the expression of measured miRNAs. The changes in hsa‑miR‑432‑5p and hsa‑miR‑194‑5p are associated with the regulation of proinflammatory pathways and RA flare-up.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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