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血清 miR-20b、miR-17-3p、HOTAIR 和 MALAT1 在糖尿病视网膜病变中的诊断和预后作用。

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

机构信息

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Fayoum, Egypt.

出版信息

IUBMB Life. 2019 Mar;71(3):310-320. doi: 10.1002/iub.1970. Epub 2018 Nov 23.

Abstract

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.

摘要

非编码 RNA 是许多疾病(包括糖尿病视网膜病变(DR))的新兴生物标志物。本研究旨在测量 DR 患者血清 miR-20b、miR-17-3p、HOTAIR 和 MALAT1 的表达水平。本研究共招募了 80 名被诊断为 2 型糖尿病(T2D)的患者和 81 名健康受试者。T2D 患者分为三组:无糖尿病性视网膜病变(NDR)组(30 例)、非增殖性糖尿病性视网膜病变(NPDR)组(30 例)和增殖性糖尿病性视网膜病变(PDR)组(20 例)。定量实时聚合酶链反应(PCR)用于评估血清 miR-20b、miR-17-3p、HOTAIR 和 MALAT1 的表达。我们发现与健康受试者相比,NDR 患者血清 miR-20b 水平显著降低,HOTAIR 和 MALAT1 水平显著升高。此外,与健康受试者相比,NPDR 和 PDR 组血清 miR-20b 和 miR-17-3p 水平显著降低,HOTAIR 和 MALAT1 水平显著升高。此外,我们发现与 NDR 患者相比,DR 患者以及 PDR 患者血清 miR-20b 和 miR-17-3p 水平显著降低,HOTAIR 和 MALAT1 水平显著升高。然而,在比较 NPDR 与 NDR 患者时,我们发现 miR-20b 和 miR-17-3p 的表达水平没有显著差异,而 NPDR 患者血清 HOTAIR 和 MALAT1 水平显著升高。此外,与 NPDR 组相比,PDR 组血清 miR-20b 和 miR-17-3p 水平显著降低,HOTAIR 和 MALAT1 水平显著升高。受试者工作特征(ROC)曲线用于评估所检查的血清非编码 RNA 作为检测 DR 严重程度的新型生化指标的诊断价值。我们的分析表明,所检查的血清非编码 RNA 可区分 DR(PDR 和 NPDR)与 NDR。此外,这些非编码 RNA(miR-17 不太重要)可作为预测 DR 严重程度的有前途的新型生物标志物,区分 PDR 与 NPDR 患者。我们可以得出结论,血清 miR-20b、miR-17-3p、HOTAIR 和 MALAT1 可作为 DR 的非侵入性生物标志物,用于 DR 的筛查和 PDR 的早期诊断。

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