Platelet-derived miR-103b as a novel biomarker for the early diagnosis of type 2 diabetes.

Abstract

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.