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食蟹猴、大鼠和人类的微小RNA表达谱比较显示,mir-182参与2型糖尿病的致病过程。

Comparative microRNA expression profiles of cynomolgus monkeys, rat, and human reveal that mir-182 is involved in T2D pathogenic processes.

作者信息

Zhou Jinghui, Meng Yuhuan, Tian Shuai, Chen Junhui, Liu Mingyu, Zhuo Min, Zhang Yu, Du Hongli, Wang Xiaoning

机构信息

School of Bioscience and Bioengineering, Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou 510006, China.

Guangdong Key Laboratory of Laboratory Animals, Guangzhou 510663, China.

出版信息

J Diabetes Res. 2014;2014:760397. doi: 10.1155/2014/760397. Epub 2014 Nov 4.

Abstract

Type 2 diabetes (T2D) is a prevalent disease that happens around the world and usually happens with insulin resistance. MicroRNAs (miRNAs) represented important roles in the suppression of gene expression and were proven to be related to human diseases. In this study, we used cynomolgus monkey fed with normal and high fatty diet (HFD), respectively, to analyze the miRNA expression profile in whole blood by deep sequencing. Finally in total 24 miRNAs with differential expression were filtered. Among them, miR-182 related to the insulin resistance by modulating FOXO1 and PI3K/AKT cascade and had the greatest copy number in the whole blood. Decrease of miR-182 in T2D cynomolgus individuals is completely consistent with the previous studies in human and rat. Integrating miR-182 tissue expression profile, target genes, and copy number in blood reveals that miR-182 plays a key role in crucial genes modulation, such as FOXO1 and BHLHE22, which leads to potential hyperglycemia and modulates the insulin secretion. In addition, miR-182 might regulate the processes of both cell proliferation and apoptosis that play crucial role in determining the cells' fate. Therefore, miR-182 can be a biomarker in diagnosis of the potential T2D that has benefits for medical purpose.

摘要

2型糖尿病(T2D)是一种在全球范围内普遍存在的疾病,通常与胰岛素抵抗相关。微小RNA(miRNA)在基因表达抑制中发挥重要作用,并且已被证明与人类疾病有关。在本研究中,我们分别用正常饮食和高脂饮食(HFD)喂养食蟹猴,通过深度测序分析全血中的miRNA表达谱。最终共筛选出24个差异表达的miRNA。其中,miR-182通过调节FOXO1和PI3K/AKT级联反应与胰岛素抵抗相关,并且在全血中的拷贝数最高。T2D食蟹猴个体中miR-182的减少与先前在人类和大鼠中的研究完全一致。整合miR-182的组织表达谱、靶基因和血液中的拷贝数表明,miR-182在调节关键基因如FOXO1和BHLHE22中起关键作用,这会导致潜在的高血糖并调节胰岛素分泌。此外,miR-182可能调节细胞增殖和凋亡过程,这在决定细胞命运中起关键作用。因此,miR-182可以作为潜在T2D诊断的生物标志物,具有医学应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7871/4235598/4dbe0badf948/JDR2014-760397.001.jpg

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