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 ... -  《-》

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 ... -  《-》

Serum miR-122 levels correlate with diabetic retinopathy.

Pastukh N ，Meerson A ，Kalish D ，Jabaly H ，Blum A ... -  《-》

Serum miRNA biomarkers serve as a fingerprint for proliferative diabetic retinopathy.

Diabetic retinopathy (DR) is a retinopathy resulting from diabetes mellitus (DM) which was classified into non-proliferative DR (NPDR) and proliferative DR (PDR). Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs) that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR. In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA). The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR) arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR. Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC) curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%. These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of PDR. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of PDR from NPDR.

Qing S ，Yuan S ，Yun C ，Hui H ，Mao P ，Wen F ，Ding Y ，Liu Q ... -  《-》

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 《-》