Circulating miR-103 family as potential biomarkers for type 2 diabetes through targeting CAV-1 and SFRP4.

Abstract

MicroRNA-103 (miR-103) family plays important roles in regulating glucose homeostasis in type 2 diabetes mellitus (DM2). However, the underlying mechanisms remain poorly characterized. The objective of this study was to test the hypothesis that circulating miR-103a and miR-103b, which regulate CAV-1 and SFRP4, respectively, are novel biomarkers for diagnosis of DM2. We determined the predictive potential of circulating miR-103a and miR-103b in pre-DM subjects (pre-DM), noncomplicated diabetic subjects, and normal glucose-tolerance individuals (control) using bioinformatic analysis, qRT-PCR, luciferase assays, and ELISA assays. We found that both miR-103a and miR-103b had high complementarity and conservation, modulated reporter gene expression through seed sequences in the 3'UTRs of CAV-1 and SFRP4 mRNA, and negatively regulated their mRNA and protein levels, respectively. We also found that increased miR-103a and decreased miR-103a in plasma were significantly and negatively correlated with reduced CAV-1 levels and elevated SFRP4 levels in pre-DM and DM2, respectively, and were significantly associated with glucose metabolism, HbA1c levels, and other DM2 risk factors for progression from a normal individual to one with pre-DM. Furthermore, we demonstrated that the reciprocal changes in circulating miR-103a and miR-103b not only provided high sensitivity and specificity to differentiate the pre-DM population but also acted as biomarkers for predicting DM2 with high diagnostic value. These findings suggest that circulating miR-103a and miR-103b may serve as novel biomarkers for diagnosis of DM2, providing novel insight into the mechanisms underlying pre-DM.