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Identification of circulating microRNAs in HNF1A-MODY carriers
1Department of Physiology and Medical Physics, Royal College of Surgeons, Dublin, Ireland.
Aims/Hypothesis:
HNF1A-MODY is a monogenic form of diabetes caused by mutations in the HNF1A gene. Here we identify, for the first time, HNF1A-MODY-associated microRNAs (miRNAs) that can be detected in the serum of HNF1A-MODY carriers.
Methods:
An miRNA array was carried out in rat INS-1 insulinoma cells inducibly expressing the common human Pro291fsinsC-HNF1A frame shift mutation. Differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of miRNAs in the serum of HNF1A-MODY carriers (n = 31), MODY-negative family members (n = 10) and individuals with type 2 diabetes mellitus (n = 17) was quantified by absolute real-time PCR analysis.
Results:
Inducible expression of Pro291fsinsC-HNF1A in INS-1 cells caused a significant upregulation of three miRNAs (miR-103, miR-224, miR-292-3p). The differential expression of two miRNAs (miR-103 and miR-224) was validated in vitro. Strongly elevated levels of miR-103 and miR-224 could be detected in the serum of HNF1A-MODY carriers compared with MODY-negative family controls. Serum levels of miR-103 distinguished HNF1A-MODY carriers from HbA1c-matched individuals with type 2 diabetes mellitus.
Conclusions/Interpretation:
Our study demonstrates that the pathophysiology of HNF1A-MODY is associated with the overexpression of miR-103 and miR-224. Furthermore, our study demonstrates that these miRNAs can be readily detected in the serum of HNF1A-MODY carriers.
Insights
Hepatocyte Nuclear Factor 1-alpha Monogenic Diabetes of Youth (HNF1A-MODY) is linked to elevated serum microRNAs (miRNAs), specifically miR-103 and miR-224. These miRNAs can be detected in carriers, aiding in HNF1A-MODY diagnosis.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Hepatocyte Nuclear Factor 1-alpha Monogenic Diabetes of Youth (HNF1A-MODY) is a genetic form of diabetes.
- Identifying biomarkers for HNF1A-MODY is crucial for early diagnosis and management.
Purpose of the Study:
- To identify specific microRNAs (miRNAs) associated with HNF1A-MODY.
- To determine if these miRNAs are detectable in the serum of HNF1A-MODY carriers.
Main Methods:
- An miRNA array was performed on rat INS-1 insulinoma cells expressing a common HNF1A mutation.
- Differentially expressed miRNAs were validated using quantitative real-time PCR.
- Serum miRNA levels were quantified in HNF1A-MODY carriers, MODY-negative controls, and individuals with type 2 diabetes mellitus.
Main Results:
- Expression of the HNF1A mutation upregulated miR-103, miR-224, and miR-292-3p in cell lines.
- miR-103 and miR-224 showed significantly elevated levels in the serum of HNF1A-MODY carriers.
- Serum miR-103 levels could differentiate HNF1A-MODY carriers from individuals with type 2 diabetes mellitus.
Conclusions:
- The pathophysiology of HNF1A-MODY involves the overexpression of miR-103 and miR-224.
- These specific miRNAs are detectable in the serum, offering potential as diagnostic biomarkers for HNF1A-MODY.
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