Gelayol Asadi1, Fatemeh Rezaei Varmaziar1, Mojgan Karimi1, Misagh Rajabinejad2, Sedigheh Ranjbar1, Ali Gorgin Karaji3, Farhad Salari3, Leila Afshar Hezarkhani4, Alireza Rezaiemanesh5. 1. Student Research Committee, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. 2. Student Research Committee, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. 3. Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. 4. Department of Neurology, School of Medicine, Farabi Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran. 5. Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: alireza.rezaiemanesh@kums.ac.ir.
Abstract
BACKGROUND: Diabetic neuropathy (DN) is one of the microvascular complications of diabetes that leads to peripheral sensorimotor and autonomic nervous system damages. In this study, we first examined the expression of lncRNA NEAT-1 and its downstream microRNAs, miR-183-5p, miR-433-3p, and then examined mRNA expression of ITGA4, ITGB1, SESN1, and SESN3 as the downstream targets of miR-183-5p, miR-433-3p. METHODS: The blood sample was obtained from a total of 40 patients with type 2 diabetes (20 DN patients and 20 non-DN diabetic cases) and ten healthy individuals. After RNA extraction from peripheral blood samples and cDNA synthesis, expression measurements were performed by the RT-qPCR technique. RESULTS: Our results showed that the expression level of lncRNA NEAT-1 was significantly higher, and the expression level of miR-183-5p was significantly lower in DN patients compared to the healthy control group. Besides, the expression level of miR-433-3p was significantly lower, and the mRNA expression of ITGA4, SESN1, and SESN3 was significantly higher in DN patients compared to the diabetes group. The ROC curve analysis showed that the miR-183-5p with high levels of accuracy could discriminate DN patients from healthy control (AUC = 0.836) and NEAT-1, SESN1, SESN3, ITGA4 have a high ability to distinguish DN from non-DN patients (AUC = 0.701, 0.772, 0.815 and 0.780, respectively). CONCLUSION: It seems that the NEAT-1 probably targets miR-183-5p and miR-433-3p, as a result of which the expression of ITGA4, SESN1, and SESN3 is affected. Dysregulated expression of NEAT-1 and related miRNAs and genes might be involved in the pathogenesis of DN.
BACKGROUND: Diabetic neuropathy (DN) is one of the microvascular complications of diabetes that leads to peripheral sensorimotor and autonomic nervous system damages. In this study, we first examined the expression of lncRNA NEAT-1 and its downstream microRNAs, miR-183-5p, miR-433-3p, and then examined mRNA expression of ITGA4, ITGB1, SESN1, and SESN3 as the downstream targets of miR-183-5p, miR-433-3p. METHODS: The blood sample was obtained from a total of 40 patients with type 2 diabetes (20 DN patients and 20 non-DN diabetic cases) and ten healthy individuals. After RNA extraction from peripheral blood samples and cDNA synthesis, expression measurements were performed by the RT-qPCR technique. RESULTS: Our results showed that the expression level of lncRNA NEAT-1 was significantly higher, and the expression level of miR-183-5p was significantly lower in DN patients compared to the healthy control group. Besides, the expression level of miR-433-3p was significantly lower, and the mRNA expression of ITGA4, SESN1, and SESN3 was significantly higher in DN patients compared to the diabetes group. The ROC curve analysis showed that the miR-183-5p with high levels of accuracy could discriminate DN patients from healthy control (AUC = 0.836) and NEAT-1, SESN1, SESN3, ITGA4 have a high ability to distinguish DN from non-DN patients (AUC = 0.701, 0.772, 0.815 and 0.780, respectively). CONCLUSION: It seems that the NEAT-1 probably targets miR-183-5p and miR-433-3p, as a result of which the expression of ITGA4, SESN1, and SESN3 is affected. Dysregulated expression of NEAT-1 and related miRNAs and genes might be involved in the pathogenesis of DN.