High level of lncRNA NR2F1-AS1 predict the onset and progression of diabetic retinopathy in type 2 diabetes.

This study aimed to investigate whether dysregulation of NR2F1-AS1 is associated with the T2D onset and DR progression. A total of 269 individuals diagnosed with T2D were recruited in this study, including 111 individuals with uncomplicated T2D and 158 individuals with nonproliferative diabetic retinopathy (NPDR). A total of 48 among the NPDR individuals developed into proliferative diabetic retinopathy (PDR), excepting that 6 individuals were dropped out. RT-qPCR was used to determine the expression of NR2F1-AS1 level in blood. The correlations between NR2F1-AS1 expression and other parameters were tested by Pearson correlation. Receiver operating characteristic (ROC) curves were plotted for evaluating the diagnostic value of NR2F1-AS1 as a biochemical indicator detecting T2D and PDR. Kaplan-Meier method and Cox multivariable analysis was used to evaluate the predictive power of NR2F1-AS1 for incidence of PDR. A significant increase in blood NR2F1-AS1 in uncomplicated T2D, NPDR, and PDR patients was found when compared to healthy subjects. Significant correlations between NR2F1-AS1 expression and the level of fasting glucose, 2-h postprandial blood glucose, and HbA1c were revealed. Furthermore, NR2F1-AS1 represented distinguishing ability in T2D individuals from healthy subjects and PDR individuals from NPDR individuals. NR2F1-AS1 also showed strong predictive ability for PDR. The examination of blood NR2F1-AS1 may be used as a noninvasive biomarker for screening of T2D and early diagnosis of DR. NR2F1-AS1 may also be used as a promising novel biomarker for prediction PDR. NR2F1-AS1 may play a role in the progression of DR by moderating EndMT.

Ji X ，Sun J ，Wang Z 《-》

Diagnostic and prognostic role of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 in diabetic retinopathy.

Noncoding RNAs are emerging biomarkers for many diseases including diabetic retinopathy (DR). This study aimed to measure the expression levels of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 in DR patients. A total of 80 patients diagnosed as type 2 diabetes (T2D) and 81 healthy subjects were recruited in this study. T2D patients were divided into three groups: nondiabetic retinopathy (NDR) group (30 patients), nonproliferative diabetic retinopathy (NPDR) group (30 patients), and proliferative diabetic retinopathy (PDR) group (20 patients). Quantitative real-time polymerase chain reaction (PCR) was used to assess the expression of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1. We found a significant decrease in serum miR-20b and a significant increase in serum HOTAIR and MALAT1 in NDR patients compared to healthy subjects. Also, we revealed a significant decrease in serum miR-20b and miR-17-3p and a significant increase in serum HOTAIR and MALAT1 in each of NPDR and PDR groups when compared with healthy subjects. Furthermore, we reported a significant decrease in miR-20b and miR-17-3p and a significant increase in HOTAIR and MALAT1in DR as well as in PDR patients when compared with NDR patients. However, on comparing NPDR with NDR patients, no significant difference was observed regarding the expression levels of miR-20b and miR-17-3p, in contrast, significant elevation of serum HOTAIR and MALAT1 was found in NPDR. Moreover, we observed a significant decrease in serum miR-20b and miR-17-3p and a significant increase in serum HOTAIR and MALAT1 in PDR group relative to NPDR group. Receiver operating characteristic (ROC) curve was used for evaluating the diagnostic value of the examined serum noncoding RNAs as novel biochemical indicators detecting severity of DR. Our analyses suggested that the examined serum noncoding RNAs may discriminate DR (PDR and NPDR) from NDR. Furthermore, these noncoding RNAs (less importantly miR-17) can be used as promising novel biomarkers for prediction DR severity, distinguishing PDR from NPDR patients. We can conclude that serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 may be used as noninvasive biomarkers for screening of DR and early diagnosis of PDR. © 2018 IUBMB Life, 71(3):310-320, 2019.

Shaker OG ，Abdelaleem OO ，Mahmoud RH ，Abdelghaffar NK ，Ahmed TI ，Said OM ，Zaki OM ... -  《-》

Association between lncRNAs in plasma exosomes and diabetic retinopathy.

Long noncoding RNA (lncRNA) in plasma exosomes is a potential non-invasive diagnostic biomarker for diabetic retinopathy (DR). However, the changes in plasma exosomal lncRNAs and diagnostic relevance in patients with DR patients remain unclear. A case-control study with type 2 diabetes mellitus (T2DM) and patients with comorbid DR were enrolled, and their clinical information and blood samples were collected. Plasma exosomes were extracted, and the relative expression levels of representative differentially expressed exosomal lncRNAs were determined. A logistic regression model was used to analyze the relationships of DR with relative lncRNA expression and DR-related factors, and receiver operating characteristic (ROC) curve analysis was used to evaluate the value of exosomal lncRNAs for DR diagnosis. Sixty-two patients with T2DM and sixty-two patients with DR were matched by age, sex, and disease duration. The fasting blood glucose concentration, glycosylated hemoglobin level (HbA1c), and relative expression of the plasma exosomal lncRNA DLX6-AS1 were significantly higher in the DR group than in the T2DM group, whereas the 2-h C-peptide concentration and relative expression of the lncRNAs PRINS and FAM190A-3 were lower in the DR group. After adjusting for relevant confounders, the fasting blood glucose concentration, HbA1c level, 2-h C-peptide concentration, and relative expression of lncRNA DLX6-AS1, PRINS, and FAM190A-3 were found to be associated with DR. Both DLX6-AS1 [area under the curve (AUC): 0.658 (0.562-0.754)], PRINS [AUC: 0.798 (0.722-0.873)], and FAM190A-3 [AUC: 0.603 (0.503-0.702)] expression had predictive value for DR diagnosis. The combination of DLX6-AS1 and PRINS yielded an AUC of 0.813 (0.740-0.886). In males, the combination of DLX6-AS1 and PRINS yielded an AUC of 0.860 (0.780-0.940). The fasting blood glucose concentration, HbA1c level, and exosomal DLX6-AS1 expression were identified as risk factors for DR, whereas the 2-h C-peptide concentration and exosomal PRINS and FAM190A-3 were identified as protective against DR. The combination of exosomal DLX6-AS1 and PRINS had good diagnostic value for DR in the general population and males. More attention should be paid to the role of exosomal PRINS expression as a predictive and diagnostic DR biomarker in females.

Ye Q ，Li L ，Shao Z ，Xu M ，Li L ，Yan Q ，Huang B ，Zhao T ... -  《Frontiers in Endocrinology》

Potential value of lncRNAs as a biomarker for proliferative diabetic retinopathy.

To investigate the differences in lncRNAs expression in whole blood between diabetic retinopathy (DR) patients and healthy subjects, and to evaluate the potential value of lncRNAs as a diagnostic biomarker for proliferative diabetic retinopathy (PDR). A series of 34 PDR patients, 34 patients with non-proliferative DR (NPDR) and 34 healthy participants were enroled. Differentially expressed lncRNAs were demonstrated using high-throughput sequencing and validated using qRT-PCR. Gene Ontology (GO) was performed to explore the possible biological function of the differentially expressed lncRNAs. lncRNA/mRNA coexpression network was built to determine the targets of differentially expressed lncRNAs. Receiver operating characteristic (ROC) analysis was utilized to evaluate the diagnostic value of lncRNAs for PDR. We identified 175 and 179 differentially expressed lncRNAs in PDR patients compared with control samples and NPDR patients, respectively. GO analysis showed that the various metabolic processes were possibly influenced by these dysregulated lncRNAs. Using the differently expressed lncRNAs data, we further identified 82 overlapping lncRNAs in PDR patients with NPDR and control subjects. Part of these overlapping lncRNAs was significantly correlated with nuclear factor kappa B (NF-κB) and Wnt signal pathways. ROC curves were constructed for two upregulated lncRNAs and the ROC analysis indicated that both of them had potential diagnostic value and could distinguish PDR from control subjects and NPDR patients. LncRNAs expression was altered in PDR patients compared with NPDR and control subjects. Moreover, it provides a resource that lncRNAs might be novel diagnostic and prognostic biomarker for PDR.

Liu B ，Cong C ，Ma Y ，Ma X ，Zhang H ，Wang J ... -  《-》

Plasma miR-21 expression: an indicator for the severity of Type 2 diabetes with diabetic retinopathy.

To investigate the roles of plasma miR-21 in the pathogenic process of Type 2 diabetes (T2D) with diabetic retinopathy (DR). T2D patients included patients without DR (NDR) group, patients with non-proliferative/background DR (BDR) group and patients with proliferative DR (PDR) group. Healthy individuals served as control group. Fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c), triacylglycerol (TG), total cholesterol (TC), urine creatinine (Cr), fasting blood glucose (FBG), blood urea nitrogen (BUN), low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS) and plasma miR-21 expression were measured. Quantitative real-time PCR (qRT-PCR) was applied to detect miR-21 expression. Pearson analysis was used to conduct correlation analysis and receiver operating characteristic (ROC) curve was used to analyse the diagnostic value of miR-21 in T2D with DR. Compared with the control group, FBG and HbA1c increased in the NDR group; compared with the control and NDR groups, disease course, HbA1c, FPG levels and homoeostasis model assessment of insulin resistance (HOMA-IR) were increased in the BDR and PDR groups; and compared with the BDR group, disease course, HbA1c and FPG levels were higher in the PDR group. miR-21 expression was higher in the BDR group than the control group, and higher in the PDR group than the BDR group. miR-21 expression was positively related with disease course, HbA1C, FPG and HOMA-IR, and had diagnostic value for T2D with DR and PDR. The plasma miR-21 expression was increased in the development of T2D with DR and can be used as an indicator for the severity of T2D with DR.

Jiang Q ，Lyu XM ，Yuan Y ，Wang L ... -  《-》