miR‑124‑3p regulates angiogenesis in peripheral arterial disease by targeting STAT3.

miR‑124‑3p regulates angiogenesis in peripheral arterial disease by targeting STAT3.
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miR-124-3p 通过靶向 STAT3 调节外周动脉疾病的血管生成

DOI:
10.3892/mmr.2020.11538
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发表时间:
2020-12
影响因子:
3.4
通讯作者:
Jian W
Jian W
中科院分区:
医学4区
文献类型:
--
作者:
Shi Y;Xu X;Luan P;Kou W;Li M;Yu Q;Zhuang J;Xu Y;Peng W;Jian W

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外周动脉疾病(PAD)是全球第三大心血管疾病,仅次于冠状动脉疾病和中风。作为基因表达的内源性调节因子,microRNAs (miRs)参与多种疾病的发生和进展,包括癌症、自身免疫性疾病和心脏病。本研究探讨miR-124-3p在PAD中的作用。逆转录-定量PCR结果显示,miR-124-3p在后肢缺血(HLI)模型缺血组织和缺氧人脐静脉内皮细胞中的表达水平较对照组显著升高。增殖、伤口愈合和成管实验表明miR-124-3p在体外抑制血管生成,HLI模型显示miR-124-3p在体内具有相同的功能。双荧光素酶报告基因揭示STAT3是miR-124-3p的靶标。miR-124-3p在人血液中的表达水平与踝肱指数呈负相关,踝肱指数是评价PAD严重程度的指标。总之,本研究表明miR-124-3p是PAD血管生成的关键调节因子,是PAD潜在的诊断、预后和治疗靶点。
Peripheral arterial disease (PAD) is the third leading cause of cardiovascular morbidity worldwide, after coronary artery disease and stroke. As endogenous regulators of gene expression, microRNAs (miRs) are implicated in the development and progression of various diseases, including types of cancer, autoimmune diseases and heart diseases. In the present study, the role of miR-124-3p in PAD was investigated. The reverse transcription-quantitative PCR results indicated that the expression levels of miR-124-3p were significantly increased in the ischemic tissue of the hindlimb ischemia (HLI) model and in hypoxic human umbilical vein endothelial cells compared with the corresponding control groups. Proliferation, wound healing and tube formation assays demonstrated the inhibition of miR-124-3p on angiogenesis in vitro and the HLI model indicated the same function of miR-124-3p in vivo. A dual-luciferase reporter revealed STAT3 as the target of miR-124-3p. The expression levels of miR-124-3p in human blood were negatively correlated with ankle-brachial index, which is an index for the evaluation of the severity of PAD. Collectively, the present study indicated that miR-124-3p was a critical regulator of angiogenesis in PAD, and a potential diagnostic, prognostic and therapeutic target for PAD.
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