Mao Luo1,2, Chunrong Xu1,2, Yulin Luo3, Gang Wang1,2, Jianbo Wu1,2, Qin Wan4. 1. Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China. 2. Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China. 3. GCP Center, Affiliated Hospital (T.C.M) of Southwest Medical University, Luzhou, Sichuan, China. 4. Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. wanqin3@126.com.
Abstract
AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Entities:
Keywords:
Caveolin-1; Circulating microRNA; Pre-diabetes; Secreted frizzled-related protein 4; Type 2 diabetes mellitus
Authors: Pads Palihaderu; Bilm Mendis; Jmkjk Premarathne; Wkrr Dias; Swee Keong Yeap; Wan Yong Ho; A S Dissanayake; I H Rajapakse; P Karunanayake; U Senarath; D A Satharasinghe Journal: Epigenet Insights Date: 2022-10-15