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miR‐23b‐3p and miR‐125b‐5p downregulate apo(a) expression by targeting Ets1 in HepG2 cells

机译:miR-23b-3p和miR-125b-5p通过靶向epg2细胞中的ETS1来下调apo(a)表达

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摘要

Abstract High concentrations of plasma lipoprotein(a) [Lp(a)] have been inferred to be an independent risk factor for cardiovascular and cerebrovascular diseases, such as coronary artery diseases, restenosis, and stroke. Apolipoprotein(a) [apo(a)] is one of the most important components of Lp(a) and contributes greatly to the increased concentration of plasma Lp(a). As a critical positive transacting factor of apo(a) gene, Ets1 has been proven as a target gene of several miRNAs, such as miR‐193b, miR‐125b‐5p, miR‐200b, miR‐1, and miR‐499. In this study, a series of experiments on miRNAs and relative miRNAs inhibitor delivered HepG2 cells were conducted, and two miRNAs that downregulate the apo(a) by targeting the 3′‐UTR of Ets1 were identified. Results showed that apo(a) and Ets1 were differentially expressed in SMMC7721 and HepG2 cell lines. Meanwhile, apo(a) and Ets1 were inversely correlated with several hepatic endogenous miRNAs, such as miR‐125b‐5p, miR‐23b‐3p, miR‐26a‐5p, and miR‐423‐5p, which were predicted to bind to Ets1. Results show that miR‐125b‐5p and miR‐23b‐3p mimics could inhibit the synthesis of apo(a) by directly targeting Ets1 in HepG2, thereby reducing the plasma Lp (a) concentration.
机译:摘要高浓度血浆脂蛋白(a)[Lp(a)]被认为是心脑血管疾病的独立危险因素,如冠状动脉疾病、再狭窄和中风。载脂蛋白(a)[apo(a)]是Lp(a)最重要的成分之一,对血浆Lp(a)浓度的升高有很大的贡献。Ets1作为载脂蛋白(a)基因的一个关键正转录因子,已被证明是几种miRNA的靶基因,如miR-193b、miR-125b-5p、miR-200b、miR-1和miR-499。在这项研究中,对miRNA和相关的miRNA抑制剂递送的HepG2细胞进行了一系列实验,并鉴定出两种通过靶向Ets1的3′-UTR下调载脂蛋白(a)的miRNA。结果表明,apo(a)和Ets1在SMMC7721和HepG2细胞系中差异表达。同时,载脂蛋白(a)和Ets1与几种肝脏内源性miRNA呈负相关,如miR-125b-5p、miR-23b-3p、miR-26a-5p和miR-423-5p,它们被预测与Ets1结合。结果表明,miR-125b-5p和miR-23b-3p模拟物可以通过直接靶向HepG2中的Ets1来抑制载脂蛋白(a)的合成,从而降低血浆Lp(a)浓度。

著录项

  • 来源
    《Cell biology international.》 |2018年第3期|共11页
  • 作者单位

    The Second Hospital Affiliated to University of South ChinaHengyang Hunan 421001 PR China;

    Institute of Cardiovascular Research Key Laboratory for Atherosclerology of Hunan;

    The Second Hospital Affiliated to University of South ChinaHengyang Hunan 421001 PR China;

    Institute of Cardiovascular Research Key Laboratory for Atherosclerology of Hunan;

    Institute of Cardiovascular Research Key Laboratory for Atherosclerology of Hunan;

    Institute of Cardiovascular Research Key Laboratory for Atherosclerology of Hunan;

    The First Hospital Affiliated to University of South ChinaHengyang Hunan 421001 PR China;

    Institute of Cardiovascular Research Key Laboratory for Atherosclerology of Hunan;

    Institute of Cardiovascular Research Key Laboratory for Atherosclerology of Hunan;

    Institute of Cardiovascular Research Key Laboratory for Atherosclerology of Hunan;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    atherosclerosis; Lipoprotein (a); miR‐23b‐3p; miR‐125b‐5p;

    机译:动脉粥样硬化;脂蛋白(a);mir-23b-3p;mir-125b-5p;

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