Shahin Alizadeh-Fanalou1, Fatemeh Alian2, Mina Mohammadhosayni3, Dariush Rahban4, Pedram Abbasi Ghasem Kheyli5, Majid Ahmadi6. 1. Student Research Committee, Iran University of Medical Sciences, Tehran, Iran; Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. 2. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. 3. Department of Immunology, Faculty of Medicine, Shahed University, Tehran, Iran. 4. Department of Nanomedicine, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Poursina St., Tehran, Iran. Electronic address: rahbandariush@gmail.com. 5. Paramedical Department, Shiraz University of Medical Sciences, Shiraz, Iran. 6. Stem Cell Research Center, Tabriz University of Medical Sciences, Daneshghah St., Imam Reza Hospital, Tabriz, Iran; Student's Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: ahmadi.m@tbzmed.ac.ir.
Abstract
BACKGROUND: Impaired elimination mechanisms of the autoreactive lymphocytes, like T lymphocytes, via apoptosis may be the cause of continues inflammatory state in multiple sclerosis (MS). BIRC5 gene codify for the survivin, which participates in the modulation of apoptosis and cell survival. The objective of this study was investigation of the role of important confirmed miRNAs, including miR-335, miR-485, miR-542, and miR-708, in the regulation of survivin mRNA in the CD4+ T cells of MS cases. METHODS: In this study, 50 RRMS patients as well as 50 healthy matched controls were recruited. The peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples and CD4+ T cells were prepared. After that, RNA was extracted, cDNA was synthesized, and the expression levels of miR-335, miR-485, miR-542, and miR-708 were measured using Real-time PCR. Moreover, the mRNA expression of survivin was detected. Serum level of survivin was detected using ELISA. RESULTS: The mRNA of survivin was 2-folds upregulated in the CD4+ T cells from MS patients in comparison to the healthy controls (P = 0.0053). Serum level of survivin was higher in patients than controls. There was statistically significant downregulation of miR-485 (P = 0.001) and miR-708 (P = 0.011) in CD4+ T cells of patients compared with controls. The miR-485 downregulation had statistically significant correlation with the mRNA expression and serum level of survivin. CONCLUSION: miRNAs play a role in the regulation of survivin, and therefore apoptosis of CD4+ T cells, and hence are probably participating in a persistent inflammatory condition in MS patients.
BACKGROUND: Impaired elimination mechanisms of the autoreactive lymphocytes, like T lymphocytes, via apoptosis may be the cause of continues inflammatory state in multiple sclerosis (MS). BIRC5 gene codify for the survivin, which participates in the modulation of apoptosis and cell survival. The objective of this study was investigation of the role of important confirmed miRNAs, including miR-335, miR-485, miR-542, and miR-708, in the regulation of survivin mRNA in the CD4+ T cells of MS cases. METHODS: In this study, 50 RRMS patients as well as 50 healthy matched controls were recruited. The peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples and CD4+ T cells were prepared. After that, RNA was extracted, cDNA was synthesized, and the expression levels of miR-335, miR-485, miR-542, and miR-708 were measured using Real-time PCR. Moreover, the mRNA expression of survivin was detected. Serum level of survivin was detected using ELISA. RESULTS: The mRNA of survivin was 2-folds upregulated in the CD4+ T cells from MS patients in comparison to the healthy controls (P = 0.0053). Serum level of survivin was higher in patients than controls. There was statistically significant downregulation of miR-485 (P = 0.001) and miR-708 (P = 0.011) in CD4+ T cells of patients compared with controls. The miR-485 downregulation had statistically significant correlation with the mRNA expression and serum level of survivin. CONCLUSION: miRNAs play a role in the regulation of survivin, and therefore apoptosis of CD4+ T cells, and hence are probably participating in a persistent inflammatory condition in MS patients.
Authors: Enrique González-Madrid; Ma Andreina Rangel-Ramírez; María José Mendoza-León; Oscar Álvarez-Mardones; Pablo A González; Alexis M Kalergis; Ma Cecilia Opazo; Claudia A Riedel Journal: Int J Mol Sci Date: 2022-06-25 Impact factor: 6.208