Rajabinejad Misagh, Asadi Gelayol, Ranjbar Sedigheh, Varmaziar Fatemeh Rezaei, Karimi Mojgan, Salari Farhad, Karaji Ali Gorgin, Rezaiemanesh Alireza, Hezarkhani Leila Afshar
Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
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.
Immunol Lett. 2022 May;245:69-78. doi: 10.1016/j.imlet.2022.03.004. Epub 2022 Apr 7.
Diabetic neuropathy (DN) is one of the most common microvascular complications of diabetes that is attributed to impaired immune regulation. In this study, we first examined the expression of long non-coding (lncRNAs) MALAT1 and H19, and their downstream microRNAs (miRNAs) miR-19b-3p, miR-125a-5p, and then assayed the mRNA expression of downstream targets of these miRNAs, including SEMA4C, SEMA4D, PLXNB2, ATG14, and ATG16L1.
Peripheral blood samples were obtained from 20 DN patients, 20 diabetic patients without neuropathy (non-DN), and 10 healthy controls (HC). The expression levels of lncRNAs, miRNAs, and target genes were evaluated in whole blood using Real-time PCR.
Upregulation of MALAT1, H19, SEMA4C, PLXNB2, and ATG16L1 and downregulation of miR-19b-3p was seen in the DN group compared to the non-DN and HC groups. Non-DN patients had significantly lower expression levels of miR-125a-5p, SEMA4D, ATG14, and ATG16L1 compared to the HC. MALAT1 and H19 had a positive correlation with each other and had a negative correlation with the expression of miR-19b-3p. Expression levels of SEMA4C, SEMA4D, PLXNB2, and ATG16L1 were positively correlated with each other as well as lncRNAs expression. Receiver operating characteristic (ROC) analysis showed Area under the curve (AUC) = 0.9226 for MALAT1, AUC= 0.9248 for H19, and AUC= 0.7683 for miR-19b-3p.
The MALAT1-H19/miR-19b-3p axis might be involved in the development of DN and these molecules could be useful biomarkers for DN. Dysregulated expression of SEMA4C, PLXNB2, and ATG16L1, targeted by miR-19b-3p and miR-125a-5p, showed that they probably play a role in the DN development.
糖尿病神经病变（DN）是糖尿病最常见的微血管并发症之一，其归因于免疫调节受损。在本研究中，我们首先检测了长链非编码（lncRNAs）MALAT1和H19及其下游微小RNA（miRNAs）miR-19b-3p、miR-125a-5p的表达，然后测定了这些miRNAs下游靶标的mRNA表达，包括SEMA4C、SEMA4D、PLXNB2、ATG14和ATG16L1。
采集20例DN患者、20例无神经病变的糖尿病患者（非DN）和10例健康对照（HC）的外周血样本。使用实时PCR评估全血中lncRNAs、miRNAs和靶基因的表达水平。
与非DN组和HC组相比，DN组中MALAT1、H19、SEMA4C、PLXNB2和ATG16L1上调，miR-19b-3p下调。与HC相比，非DN患者的miR-125a-5p、SEMA4D、ATG14和ATG16L1表达水平显著降低。MALAT1和H19相互呈正相关，与miR-19b-3p的表达呈负相关。SEMA4C、SEMA4D、PLXNB2和ATG16L1的表达水平相互之间以及与lncRNAs表达呈正相关。受试者工作特征（ROC）分析显示，MALAT1的曲线下面积（AUC）=0.9226，H19的AUC=0.9248，miR-19b-3p的AUC=0.7683。
MALAT1-H19/miR-19b-3p轴可能参与DN的发生发展，这些分子可能是DN的有用生物标志物。miR-19b-3p和miR-125a-5p靶向的SEMA4C、PLXNB2和ATG16L1表达失调，表明它们可能在DN的发生发展中起作用。
