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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:We undertook a prospective temporal study collecting blood samples from consenting pregnant women, to test the hypothesis that circulating extracellular vesicles (EVs) carrying specific non-coding microRNA signatures can underlie gestational diabetes mellitus (GDM). To test this hypothesis, miRNA cargo of isolated and characterized EVs revealed contributions from the placenta and differential expression at all three trimesters and at delivery between pregnant and non-pregnant states. Many miRNAs originate from the placental-specific chromosome 19 microRNA cluster (19MC) and chromosome 14 microRNA cluster (14MC). Further a positive correlation emerged between third trimester and at delivery EVs containing miRNAs and those expressed by the corresponding post-parturient placentas (R value = 0.63 to 0.69, p value = 2.2X10-16), in normal and GDM. In addition, distinct differences at all trimesters emerged between women who subsequently developed GDM. Analysis by logistic regression with leave-one-out-cross validation revealed the optimal combination of miRNAs using all the circulating miRNAs (miR-92a-3p, miR-192-5p, miR-451a, miR-122-5p), or using only the differentially expressed miRNAs (has-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-100-5p and hsa-miR-125a-3p) in GDM during the first trimester. As an initial step, both sets of miRNAs demonstrated a predictive probability with an area under the curve of 0.95 to 0.96. These miRNAs targeted genes involved in cell metabolism, proliferation and immune tolerance. In particular genes of the P-I-3-Kinase, FOXO, insulin signaling and glucogenic pathways were targeted, suggestive of placental connectivity with various maternal organs/cells, altering physiology along with pathogenic mechanisms underlying the subsequent development of GDM. We conclude that circulating EVs originating from the placenta with their miRNA cargo communicate and regulate signaling pathways in maternal organs, thereby predetermining development of GDM.

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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