Identification of circulating microRNAs in HNF1A-MODY carriers

25Citations
Citations of this article
48Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

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. © 2013 Springer-Verlag Berlin Heidelberg.

Author supplied keywords

Cite

CITATION STYLE

APA

Bonner, C., Nyhan, K. C., Bacon, S., Kyithar, M. P., Schmid, J., Concannon, C. G., … Byrne, M. M. (2013). Identification of circulating microRNAs in HNF1A-MODY carriers. Diabetologia, 56(8), 1743–1751. https://doi.org/10.1007/s00125-013-2939-4

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free