Identification of stress‐related microRNA biomarkers in type 2 diabetes mellitus: A systematic review and meta‐analysis

• Published in: Journal of diabetes 2020-09, Vol.12 (9), p.633-644
• Main Authors: Liang, Ying‐Zhi, Li, Jia‐Jiang‐Hui, Xiao, Huan‐Bo, He, Yan, Zhang, Ling, Yan, Yu‐Xiang
• Format: Article
• Language: English
• Subjects: 2型糖尿病; Biomarkers; Diabetes; Meta-analysis; meta分析; microRNA; MicroRNAs; miRNA; review; Sensitivity analysis; stress; type 2 diabetes mellitus; 应激; 综述
• ISSN: 1753-0393; 1753-0407
• DOI: 10.1111/1753-0407.12643

Background Many studies have investigated microRNAs (miRNAs) in the detection of type 2 diabetes mellitus (T2DM). Herein, the dysregulated direction of stress‐related miRNAs used as biomarkers of T2DM are summarized and analyzed. Methods PubMed, EMBASE, ISI Web of Science, and three Chinese databases were searched for case–control miRNA profiling studies about T2DM. A meta‐analysis under a random effect was performed. Subgroup analysis was conducted based on different tissues and species. Sensitivity analysis was conducted to confirm the robustness among studies. The effect size was pooled using ln odds ratios (ORs), 95% confidence intervals (95% CIs), and P‐values. Results The present meta‐analysis included 39 case–control studies with a total of 494 miRNAs. Only 33 miRNAs were reported in three or more studies and, of these, 18 were inconsistent in their direction of dysregulation. Two significantly dysregulated miRNAs (let‐7 g and miR‐155) were identified in the meta‐analysis. Four miRNAs (miR‐142‐3p, miR‐155, miR‐21, and miR‐34c‐5p) were dysregulated in patients with T2DM, whereas five miRNAs (miR‐146a, miR‐199a‐3p, miR‐200b, miR‐29b and miR‐30e) were dysregulated in animal models of diabetes. In addition, two dysregulated miRNAs (miR‐146a and miR‐21) were highly cornea specific and heart specific. In sensitivity analysis, only miR‐155 was still significantly dysregulated after removing studies with small sample sizes. Conclusions The present meta‐analysis revealed that 16 stress‐related miRNAs were significantly dysregulated in T2DM. MiR‐148b, miR‐223, miR‐130a, miR‐19a, miR‐26b and miR‐27b were selected as potential circulating biomarkers of T2DM. In addition, miR‐146a and miR‐21 were identified as potential tissue biomarkers of T2DM. 摘要 背景 已有多个研究发现microRNAs(miRNAs)可以作为2型糖尿病的生物标志物, 本文对其中表达失调的应激相关miRNAs进行了归纳和分析。 方法 按检索策略, 系统检索PubMed、EMBASE、ISI Web of Science以及三个中文文献数据库中2型糖尿病相关miRNAs的病例‐对照研究。采用随机效应模型进行meta分析, 并根据样本来自的物种和组织进行亚组分析。通过敏感性分析以确认研究结果的稳定性。使用lnORs、95% CI以及P值估计总效应量。 结果 最终研究纳入了39篇文献包括494个应激相关miRNAs。在3个及以上研究中均被报道的仅有33个miRNAs, 其中18个表达变化方向不一致, 通过meta分析, 确定其中let‐7g和 miR‐155与2型糖尿病显著关联。亚组分析显示, miR‐142‐3p、miR‐155、miR‐21和miR‐34c‐5p在2型糖尿病患者中的表达有显著性差异, miR‐146a、miR‐199a‐3p、miR‐200b、miR‐29b和miR‐30e在2型糖尿病动物模型中的表达有显著性差异。此外, miR‐146a和miR‐21分别具有角膜及心脏组织特异性。敏感性分析结果显示仅miR‐155与总体分析结果一致。 结论 本研究发现16个应激相关miRNAs在2型糖尿病中存在显著表达失调。其中miR‐148b、miR‐223、miR‐130a、miR‐19a、miR‐26b和miR‐27b可作为潜在的循环标志物, miR‐146a和miR‐21则可作为潜在的组织生物标志物。 Highlights Six microRNAs (miR‐148b, miR‐223, miR‐