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

Abstract

// Xin Deng 1, 2, * , Yaofang Liu 3, * , Mao Luo 1, 2 , Jian Wu 4 , Rongyue Ma 5 , Qin Wan 6 and Jianbo Wu 1, 2 1 Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China 2 Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China 3 Department of Gynaecology and Obstetrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China 4 Medical Research Center, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China 5 The Lee Woo Sing College, Chinese University of Hong Kong, Sha Tin, Hong Kong 6 Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China * Xin Deng and Yaofang Liu contributed equally to this work Correspondence to: Jianbo Wu, email: jbwucn1996@yahoo.com Qin Wan, email: wanqin3@163.com Keywords: biomarker, circulating miR-24, coronary heart disease, YKL-40, type 2 diabetes Received: January 19, 2017     Accepted: May 23, 2017     Published: June 21, 2017 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.