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微小RNA在代谢性疾病中的作用

The Role of miRNAs in Metabolic Diseases.

作者信息

Macvanin Mirjana, Obradovic Milan, Zafirovic Sonja, Stanimirovic Julijana, Isenovic Esma R

机构信息

Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.

出版信息

Curr Med Chem. 2023;30(17):1922-1944. doi: 10.2174/0929867329666220801161536.

DOI:10.2174/0929867329666220801161536
PMID:35927902
Abstract

Metabolic diseases such as obesity, diabetes, dyslipidemia, and insulin resistance are characterized by glucose and lipid metabolism alterations and represent a global health problem. Many studies have established the crucial role of micro-ribonucleic acids (miRNAs) in controlling metabolic processes in various tissues. miRNAs are single- stranded, highly conserved non-coding RNAs containing 20-24 oligonucleotides that are expressed in a tissue-specific manner. miRNAs mainly interact through base pairing with 3' untranslated regions of target gene mRNAs to promote inhibition of their translation. miRNAs regulate the expression of as many as 30% of the human genes and have a role in crucial physiological processes such as human growth and development, cell proliferation, apoptosis, and metabolism. The number of miRNA molecules with a confirmed role in the pathogenesis of metabolic diseases is quickly expanding due to the availability of high-throughput methodologies for their identification. In this review, we present recent findings regarding the role of miRNAs as endocrine signaling molecules involved in the regulation of insulin production and fat metabolism. We discuss the potential of extracellular miRNAs present in biological fluids miRNAs as biomarkers for the prediction of diabetes and MetS. We also give an updated overview of therapeutic interventions based on antisense oligonucleotides and the CRISPR/Cas9 editing platform for manipulating levels of miRNAs involved in metabolic disorders.

摘要

肥胖、糖尿病、血脂异常和胰岛素抵抗等代谢性疾病的特征是葡萄糖和脂质代谢改变,是一个全球性的健康问题。许多研究已经证实微小核糖核酸(miRNA)在控制各种组织的代谢过程中起着关键作用。miRNA是单链、高度保守的非编码RNA,含有20-24个寡核苷酸,以组织特异性方式表达。miRNA主要通过与靶基因mRNA的3'非翻译区碱基配对相互作用,从而抑制其翻译。miRNA调控多达30%的人类基因表达,并在人类生长发育、细胞增殖、凋亡和代谢等关键生理过程中发挥作用。由于高通量鉴定方法的出现,在代谢性疾病发病机制中具有明确作用的miRNA分子数量正在迅速增加。在这篇综述中,我们介绍了关于miRNA作为参与胰岛素产生和脂肪代谢调节的内分泌信号分子的最新研究结果。我们讨论了生物体液中存在的细胞外miRNA作为糖尿病和代谢综合征预测生物标志物的潜力。我们还提供了基于反义寡核苷酸和CRISPR/Cas9编辑平台的治疗干预措施的最新概述,这些措施用于调控参与代谢紊乱的miRNA水平。

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