Asadi Gelayol, Rezaei Varmaziar Fatemeh, Karimi Mojgan, Rajabinejad Misagh, Ranjbar Sedigheh, Gorgin Karaji Ali, Salari Farhad, Afshar Hezarkhani Leila, Rezaiemanesh Alireza
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.
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.
Immunol Lett. 2021 Apr;232:20-26. doi: 10.1016/j.imlet.2021.01.007. Epub 2021 Jan 27.
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.
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.
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).
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.
糖尿病神经病变(DN)是糖尿病的微血管并发症之一,可导致周围感觉运动和自主神经系统损伤。在本研究中,我们首先检测了lncRNA NEAT-1及其下游微小RNA miR-183-5p、miR-433-3p的表达,然后检测了作为miR-183-5p、miR-433-3p下游靶点的ITGA4、ITGB1、SESN1和SESN3的mRNA表达。
共采集40例2型糖尿病患者(20例DN患者和20例非DN糖尿病患者)及10名健康个体的血样。从外周血样本中提取RNA并合成cDNA后,采用RT-qPCR技术进行表达测定。
我们的结果显示,与健康对照组相比,DN患者中lncRNA NEAT-1的表达水平显著升高,而miR-183-5p的表达水平显著降低。此外,与糖尿病组相比,DN患者中miR-433-3p的表达水平显著降低,ITGA4、SESN1和SESN3的mRNA表达显著升高。ROC曲线分析显示,高水平准确性的miR-183-5p能够区分DN患者与健康对照(AUC = 0.836),而NEAT-1、SESN1、SESN3、ITGA4区分DN患者与非DN患者的能力较高(AUC分别为0.701、0.772、0.815和0.780)。
似乎NEAT-1可能靶向miR-183-5p和miR-433-3p,从而影响ITGA4、SESN1和SESN3的表达。NEAT-1及相关miRNA和基因的表达失调可能参与了DN的发病机制。