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Circulating miR-103 family as potential biomarkers for type 2 diabetes through targeting CAV-1 and SFRP4
Mao Luo1,2, Chunrong Xu1,2, Yulin Luo3
1Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.
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.
Insights
Circulating miR-103a and miR-103b are potential biomarkers for type 2 diabetes mellitus (DM2) diagnosis. These microRNAs regulate glucose homeostasis and can predict DM2 progression, offering new diagnostic insights.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- MicroRNA-103 (miR-103) family is crucial for glucose homeostasis in type 2 diabetes mellitus (DM2).
- Mechanisms of miR-103 in DM2 pathogenesis are not fully understood.
- miR-103a and miR-103b target CAV-1 and SFRP4, respectively.
Purpose of the Study:
- To investigate circulating miR-103a and miR-103b as potential diagnostic biomarkers for DM2.
- To elucidate the role of miR-103a and miR-103b in DM2 pathogenesis.
- To assess the predictive value of these microRNAs in pre-diabetic and diabetic individuals.
Main Methods:
- Bioinformatic analysis to predict miR-103a/b targets.
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for microRNA and mRNA quantification.
- Luciferase assays to confirm target gene regulation.
- Enzyme-linked immunosorbent assays (ELISA) for protein level analysis.
- Analysis of plasma samples from individuals with normal glucose tolerance, pre-DM, and DM2.
Main Results:
- miR-103a and miR-103b negatively regulate CAV-1 and SFRP4 mRNA and protein levels.
- Plasma levels of miR-103a and miR-103b correlate with CAV-1 and SFRP4 levels in pre-DM and DM2.
- Reciprocal changes in miR-103a/b are associated with glucose metabolism, HbA1c, and DM2 risk factors.
- Circulating miR-103a/b demonstrate high sensitivity and specificity in differentiating pre-DM and predicting DM2.
Conclusions:
- Circulating miR-103a and miR-103b show promise as novel biomarkers for DM2 diagnosis.
- These microRNAs provide insights into the underlying mechanisms of pre-DM and DM2.
- Further validation may establish miR-103a/b as valuable tools in DM2 management.
