yes / Type 2 diabetes mellitus prevalence is growing globally, and the leading cause of mortality in these patients is cardiovascular
disease. Epigenetic mechanisms such as microRNAs (miRs) and DNA methylation may contribute to complications of
type 2 diabetes mellitus. We discovered an aberrant type 2 diabetes mellitus–smooth muscle cell phenotype driven by
persistent up-regulation of miR-145. This study aimed to determine whether elevated expression was due to changes
in methylation at the miR-145 promoter. Smooth muscle cells were cultured from saphenous veins of 22 non-diabetic
and 22 type 2 diabetes mellitus donors. DNA was extracted, bisulphite treated and pyrosequencing used to interrogate
methylation at 11 CpG sites within the miR-145 promoter. Inter-patient variation was high irrespective of type 2 diabetes
mellitus. Differential methylation trends were apparent between non-diabetic and type 2 diabetes mellitus–smooth
muscle cells at most sites but were not statistically significant. Methylation at CpGs −112 and −106 was consistently
lower than all other sites explored in non-diabetic and type 2 diabetes mellitus–smooth muscle cells. Finally, miR-145
expression per se was not correlated with methylation levels observed at any site. The persistent up-regulation of miR-
145 observed in type 2 diabetes mellitus–smooth muscle cells is not related to methylation at the miR-145 promoter.
Crucially, miR-145 methylation is highly variable between patients, serving as a cautionary note for future studies of this
region in primary human cell types.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/11032 |
| Date | 21 December 2016 |
| Creators | Riches-Suman, Kirsten, Huntriss, J., Keeble, C., Wood, I.C., O'Regan, D.J., Turner, N.A., Porter, K.E. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Published version |
| Rights | © The Authors 2016. Distributed under the terms of the Creative Commons Attribution 3.0 License (http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
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