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Circulating miRNA-24 and its target YKL-40 as potential biomarkers in patients with coronary heart disease and type 2 diabetes mellitus.

ABSTRACT: Type 2 diabetes mellitus (DM2) is associated with cardiovascular complications and is characterized by high levels of YKL-40, an inflammatory glycoprotein involved in endothelial dysfunction. We investigated the predictive potential of circulating miR-24 in coronary heart diseases (CHD) DM2 patients with CHD, and control subjects. Blood samples were taken from 94 subjects of both genders, and divided over three groups as follows; patients with CHD, patients with DM2 and CHD, and control subjects. Both miR-24 (using real time PCR) and routine parameters were measured. Using bioinformatic analysis and luciferase assays, we found that miR-24 has high complementarity and a high degree of species conservation with respect to the binding sites within the 3' UTR of the YKL-40 mRNA. The expression levels of circulating miR-24, determined by quantitative real time PCR, were significantly decreased in peripheral blood of DM2-CHD and CHD patients compared with controls. Furthermore, miR-24 strongly associated with DM2-CHD, negatively correlated with YKL-40 in DM2-CHD and DM2 patients after conducting multiple regression analysis. These results provide a novel regulatory mechanism of circulating miR-24 in regulating YKL-40 levels in DM2-CHD, may serve as a biomarker for predicting patients with DM2 and CHD.

SUBMITTER: Deng X

PROVIDER: S-EPMC5609901 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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Circulating miRNA-24 and its target YKL-40 as potential biomarkers in patients with coronary heart disease and type 2 diabetes mellitus.

Deng Xin X Liu Yaofang Y Luo Mao M Wu Jian J Ma Rongyue R Wan Qin Q Wu Jianbo J

Oncotarget 20170621 38

Type 2 diabetes mellitus (DM2) is associated with cardiovascular complications and is characterized by high levels of YKL-40, an inflammatory glycoprotein involved in endothelial dysfunction. We investigated the predictive potential of circulating miR-24 in coronary heart diseases (CHD) DM2 patients with CHD, and control subjects. Blood samples were taken from 94 subjects of both genders, and divided over three groups as follows; patients with CHD, patients with DM2 and CHD, and control subjects ...[more]

PMID: 28968969

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Project description:Gestational diabetes mellitus (GDM) is characterized by insulin resistance accompanied by low/absent beta-cell compensatory adaptation to the increased insulin demand. Although the molecular mechanisms and factors acting on beta-cell compensatory response during pregnancy have been partially elucidated and reported, those inducing an impaired beta-cell compensation and function, thus evolving in GDM, have yet to be fully addressed. MicroRNAs (miRNAs) are a class of small endogenous non-coding RNAs, which negatively modulate gene expression through their sequence-specific binding to 3'UTR of mRNA target. They have been described as potent modulators of cell survival and proliferation and, furthermore, as orchestrating molecules of beta-cell compensatory response and function in diabetes. Moreover, it has been reported that miRNAs can be actively secreted by cells and found in many biological fluids (e.g., serum/plasma), thus representing both optimal candidate disease biomarkers and mediators of tissues crosstalk(s). Here, we analyzed the expression profiles of circulating miRNAs in plasma samples obtained from n?=?21 GDM patients and from n?=?10 non-diabetic control pregnant women (24-33?weeks of gestation) using TaqMan array microfluidics cards followed by RT-real-time PCR single assay validation. The results highlighted the upregulation of miR-330-3p in plasma of GDM vs non-diabetics. Furthermore, the analysis of miR-330-3p expression levels revealed a bimodally distributed GDM patients group characterized by high or low circulating miR-330 expression and identified as GDM-miR-330high and GDM-miR-330low. Interestingly, GDM-miR-330high subgroup retained lower levels of insulinemia, inversely correlated to miR-330-3p expression levels, and a significant higher rate of primary cesarean sections. Finally, miR-330-3p target genes analysis revealed major modulators of beta-cell proliferation and of insulin secretion, such as the experimentally validated genes E2F1 and CDC42 as well as AGT2R2, a gene involved in the differentiation of mature beta-cells. In conclusion, we demonstrated that plasma miR-330-3p could be of help in identifying GDM patients with potential worse gestational diabetes outcome; in GDM, miR-330-3p may directly be transferred from plasma to beta-cells thus modulating key target genes involved in proliferation, differentiation, and insulin secretion.

Dataset Information

Circulating miRNA-24 and its target YKL-40 as potential biomarkers in patients with coronary heart disease and type 2 diabetes mellitus.

Publications

Circulating miRNA-24 and its target YKL-40 as potential biomarkers in patients with coronary heart disease and type 2 diabetes mellitus.

Similar Datasets

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