Exploring the role of miRNAs in the diagnosis of MODY3

Authors: OĞUZHAN FATİH BALTACI, ŞEYMA ÇOLAKOĞLU, GÖKÇE GÜLLÜ AMURAN, NESLİHAN AYDIN, MEHMET SARĞIN, ARZU KARABAY KORKMAZ, MEHMET TEMEL YILMAZ, ERGÜL BERBER

Abstract: Background/aim: MODY3 associated with HNF1A is the most common form of MODY and is clinically misdiagnosed as type 1 diabetes due to similar clinical symptoms. This study aimed to analyze the role of HNF1A-regulated miRNAs as a biomarker in the diagnosis of MODY3. Materials and methods: MIN6 cells were transfected with the HNF1A cDNA expression vector for overexpression or with siRNA specific to HNF1A to silence its expression. The HNF1A-regulated miRNAs were determined by RNA-Seq of the total RNA extract. Expressions of the candidate miRNAs in blood samples of MODY3, type 1 diabetes, and type 2 diabetes patients and in healthy subjects were compared statistically by Mann-Whitney U tests. Results: This study revealed the presence of 238 known HNF1A-regulated miRNAs in MIN6 cells. miR-129-1-3p, miR-200b-3p, and miR-378a-5p were selected as candidate miRNAs. The expression level of miR-378a-5p significantly decreased in type 2 diabetes and MODY3 patients, while miR-200b-3p expression was significantly decreased only in MODY3 patients. Conclusion: Although further studies with larger numbers of patients are required, this study demonstrated that the expression levels of miR-200b-3p and miR-378a-5p decrease in MODY3 patients and suggests that miR-200b-3p is an especially strong candidate to use clinically for selecting suspected MODY3 patients.

Keywords: Biomarker, diabetes, miRNA, MODY3, miR-200, miR-378

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