Hamidreza Ebrahimiyan1, Nima Rezaei2,3,4, Mahdi Vojdanian1, Saeed Aslani1,5, Ahmadreza Jamshidi1, Mahdi Mahmoudi1,5. 1. Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. 2. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 3. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 4. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Sheffield, UK. 5. Rheumatology Expert Group (REG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Abstract
AIM: Impaired regulation of immune tolerance results in autoimmune diseases, such as rheumatoid arthritis (RA). Survivin is an anti-apoptotic protein and can induce cellular mitosis. In the current study, we assessed the transcript level of total survivin (survivin-TS) and its three major variants and evaluated the expression level of important micro RNAs (miRNAs) involved in survivin expression regulation in RA patients. METHOD: Peripheral blood mononuclear cells (PBMCs) were isolated from 50 healthy controls and 50 RA-active patients. RNA extraction was performed and then single-strand complementary DNA was synthesized. Quantitative real-time polymerase chain reaction was used to assess the expression level of survivin-TS and its variants with effective miRNAs in PBMCs. RESULTS: Overexpression of survivin-2B (fold change = 1.57, P = 0.005), survivn-ΔEx3 (fold change = 1.93, P = 0.009) and downregulation of survivin-WT (fold change = 0.64, P = 0.0002) were found in PBMCs of patients, while messenger RNA (mRNA) expression of survivin-TS had no significant difference between RA patients and controls. Expression levels of miR-335-5p, miR-485-5p, miR-16-5p, miR-150-5p, miR-34a-5p, and miR-203a-3p were significantly increased in PBMCs from patients compared with healthy controls. In a correlation study, dysregulation of these miRNAs were not correlated with mRNA expression level of survivin. CONCLUSION: While survivin-TS was not differently expressed in RA patients, its variants had altered expression. Although miRNAs were aberrantly expressed in PBMCs from RA subjects, they did not regulate survivin-TS. miRNAs might be involved in RA pathogenesis, but not through controlling survivin.
AIM: Impaired regulation of immune tolerance results in autoimmune diseases, such as rheumatoid arthritis (RA). Survivin is an anti-apoptotic protein and can induce cellular mitosis. In the current study, we assessed the transcript level of total survivin (survivin-TS) and its three major variants and evaluated the expression level of important micro RNAs (miRNAs) involved in survivin expression regulation in RApatients. METHOD: Peripheral blood mononuclear cells (PBMCs) were isolated from 50 healthy controls and 50 RA-active patients. RNA extraction was performed and then single-strand complementary DNA was synthesized. Quantitative real-time polymerase chain reaction was used to assess the expression level of survivin-TS and its variants with effective miRNAs in PBMCs. RESULTS: Overexpression of survivin-2B (fold change = 1.57, P = 0.005), survivn-ΔEx3 (fold change = 1.93, P = 0.009) and downregulation of survivin-WT (fold change = 0.64, P = 0.0002) were found in PBMCs of patients, while messenger RNA (mRNA) expression of survivin-TS had no significant difference between RApatients and controls. Expression levels of miR-335-5p, miR-485-5p, miR-16-5p, miR-150-5p, miR-34a-5p, and miR-203a-3p were significantly increased in PBMCs from patients compared with healthy controls. In a correlation study, dysregulation of these miRNAs were not correlated with mRNA expression level of survivin. CONCLUSION: While survivin-TS was not differently expressed in RApatients, its variants had altered expression. Although miRNAs were aberrantly expressed in PBMCs from RA subjects, they did not regulate survivin-TS. miRNAs might be involved in RA pathogenesis, but not through controlling survivin.
Authors: José Javier Imas; Carlos Ruiz Zamarreño; Pablo Zubiate; Lorena Sanchez-Martín; Javier Campión; Ignacio Raúl Matías Journal: Sensors (Basel) Date: 2020-11-04 Impact factor: 3.576