Association of miR-145-5p, miR-143-3p and miR-146a-5p with Simplified Disease Activity Index in Rheumatoid Arthritis

Beatriz Teresita Martín Márquez,1,* Fernanda Isadora Corona Meraz,2,* Andrea Aguilar-Vázquez,3 Itzel Yoselin Arteaga Gallegos,4 Judith Alejandra Esparza Michel,4 Alvaro Jovanny Tovar–Cuevas,2 Milton Omar Guzmán-Ornelas,2 Roberto Carlos Rosales Gómez,2 Flavio Sandoval García,1 Oscar Pizano Martínez,1 Edy David Rubio Arellano,5 Gabriela Paola García-Ordoñez,5 Christian Juarez-Gomez,5 Mónica Vázquez-Del Mercado1 1Department of Molecular Biology and Genomics, Research Institute in Rheumatology and Musculoskeletal System (IIRSME), Health Sciences University Center (CUCS), University of Guadalajara, Guadalajara, Jalisco, Mexico; 2Department of Biomedical Sciences, Division of Health Sciences, University Center of Tonalá (Cutonalá), University of Guadalajara, Tonalá, Jalisco, Mexico; 3Secretariat of Sciences, Humanities and Technologies (SECIHTI), Mexico City, Mexico; 4Department of Rheumatology, Secretariat of Sciences, Humanities and Technologies (SECIHTI), Internal Medicine Division, New Civil Hospital Dr. Juan I. Menchaca, University of Guadalajara, Guadalajara, Jalisco, México; 5Department of Physiology, Health Sciences University Center (CUCS), University of Guadalajara, Guadalajara, Jalisco, Mexico*These authors contributed equally to this workCorrespondence: Mónica Vázquez-Del Mercado, Department of Molecular Biology and Genomics, Research Institute in Rheumatology and Musculoskeletal System (IIRSME), Health Sciences University Center (CUCS), University of Guadalajara, Guadalajara, Jalisco, Mexico, Email [email protected]: MicroRNAs (miR) have emerged as key regulatory molecules in immune response and inflammation. This study investigated the association between the plasma expression levels of miR-146a-5p, miR-143-3p, miR-145-5p and rheumatoid arthritis (RA) clinical activity measured by standard tools such as the Simplified Disease Activity Index (SDAI).Patients and Methods: Forty-eight RA patients fulfilling the EULAR/ACR 2010 criteria and 39 clinical apparently healthy subjects (HS) were included. Patients were categorized based on disease clinical activity using standard scores. Expression levels of miR were determined by RT-qPCR to be analyzed in the context of disease clinical activity, serum inflammation markers and autoantibodies such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP). Bioinformatic analysis was performed to assess gene interactions and signaling pathways.Results: The expression of miR-146a-5p showed higher expression in patients with low or moderate clinical disease activity. In addition, miR-145-5p was negatively correlated with both RF and anti-CCP antibodies. Bioinformatic analysis revealed that the miRs could simultaneously regulate myosin VI (MYO6) and connective tissue growth factor (CTGF) genes.Conclusion: Our findings suggest that the plasma levels of the analyzed miR are associated with key serological markers and low to moderate disease clinical activity in RA patients according to SDAI score. The bioinformatics data supports the potential for these miRs to regulate genes involved in RA pathology.Keywords: RA, miR, inflammation, SDAI