Luo Mao, Li Rong, Deng Xin, Ren Meiping, Chen Ni, Zeng Min, Yan Kai, Xia Jiyi, Liu Fei, Ma Weizhong, Yang Yan, Wan Qin, Wu Jianbo
Drug Discovery Reseach Center, Luzhou Medical College, Luzhou, Sichuan, China.
Department of Endocrinology, The Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan, China.
Acta Diabetol. 2015 Oct;52(5):943-9. doi: 10.1007/s00592-015-0733-0. Epub 2015 Mar 29.
MicroRNA-103 (miR-103) plays a critical role in regulating glucose homeostasis in type 2 diabetes (DM2). Recent data suggest that secreted frizzled-related protein 4 (SFRP4) serves as a potential risk biomarker for prediabetic mellitus (pre-DM) and that platelets are enriched for miR-103. The objective of this study was to test the hypothesis that platelet-derived miR-103b (miR-103-as), which regulates SFRP4, might be a novel biomarker for the early diagnosis of DM2.
We evaluated platelet miR-103b expression in healthy subjects (n = 46), pre-DM subjects (n = 48), non-complicated diabetic subjects (n = 43) and diabetes mellitus type 2-coronary heart disease subjects (n = 36), respectively, and analyzed the relationship of these levels with its target gene SFRP4.
In qRT-PCR assays, miR-103b were significantly down-regulated, and conversely, the expression of the SFRP4 gene was up-regulated in pooled leukocyte-depleted platelets and individual subjects with pre-DM. Additionally, patients who had undergone antiplatelet treatment were characterized by decreased gene expression of SFRP4 and increased levels of platelet-derived miR-103b. miR-103b modulated reporter gene expression through SFRP4 mRNA 3'-UTR seed sequence and negatively regulated its expression. Furthermore, SFRP4 mRNA and protein levels were down-regulated by a miR-103b mimic but were up-regulated by a miR-103b inhibitor.
The results suggest that platelet-derived miR-103b could negatively regulate the expression of SFRP4 mRNA/protein in pre-DM2, indicating that miR-103b could be a novel biomarker for the early diagnosis of DM2.
微小RNA-103（miR-103）在调节2型糖尿病（DM2）患者的葡萄糖稳态中起关键作用。近期数据表明，分泌型卷曲相关蛋白4（SFRP4）可能是糖尿病前期（pre-DM）的潜在风险生物标志物，且血小板中富含miR-103。本研究的目的是验证以下假设：调节SFRP4的血小板源性miR-103b（miR-103-as）可能是DM2早期诊断的新型生物标志物。
我们分别评估了健康受试者（n = 46）、糖尿病前期受试者（n = 48）、无并发症的糖尿病受试者（n = 43）和2型糖尿病合并冠心病受试者（n = 36）的血小板miR-103b表达，并分析了这些水平与其靶基因SFRP4的关系。
在qRT-PCR检测中，miR-103b显著下调，相反，在合并的去除白细胞的血小板以及糖尿病前期个体受试者中，SFRP4基因的表达上调。此外，接受抗血小板治疗的患者的特征是SFRP4基因表达降低，血小板源性miR-103b水平升高。miR-103b通过SFRP4 mRNA 3'-UTR种子序列调节报告基因表达，并对其表达产生负调控。此外，miR-103b模拟物可下调SFRP4 mRNA和蛋白水平，而miR-103b抑制剂则使其上调。
结果表明，血小板源性miR-103b可在糖尿病前期2型患者中负调控SFRP4 mRNA/蛋白的表达，表明miR-103b可能是DM2早期诊断的新型生物标志物。
