miR-34a-5p aggravates hypoxia-induced apoptosis by targeting ZEB1 in cardiomyocytes
miR-34a-5p aggravates hypoxia-induced apoptosis by targeting ZEB1 in cardiomyocytes
复制标题
miR-34a-5p 通过靶向心肌细胞中的 ZEB1 加剧缺氧诱导的细胞凋亡。
DOI：
10.1515/hsz-2018-0195
复制
发表时间：
2019-02-01
影响因子：
3.7
通讯作者：
Yu, Bo
中科院分区：
文献类型：
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作者：
Shi, Kaiyao;Sun, Huan;Yu, Bo
心肌梗死（MI）是一个尚未解决的健康问题，严重影响着全球人类健康。作为一种抑癌基因的微小核糖核酸 - 34a - 5p（miR - 34a - 5p）与左心室重构相关。我们旨在探究miR - 34a - 5p在心肌细胞中的功能作用。根据细胞活力下降和凋亡增加情况，分析缺氧诱导的H9c2细胞、HL - 1细胞以及人类心肌细胞的损伤。在氧气浓度降低时，通过定量逆转录聚合酶链反应（qRT - PCR）检测miR - 34a - 5p的表达。然后，评估异常表达的miR - 34a - 5p对缺氧培养的心肌细胞增殖和凋亡的影响。最后，探究miR - 34a - 5p的下游蛋白及信号通路。缺氧培养48小时后成功构建缺氧模型。当氧气浓度降低时，miR - 34a - 5p水平显著升高。随后，我们发现miR - 34a - 5p加剧了缺氧诱导的心肌细胞增殖和凋亡改变。锌指E盒结合同源框1（ZEB1）被确定为miR - 34a - 5p的一个靶标，miR - 34a - 5p通过靶向ZEB1发挥其功能。最后，抑制miR - 34a - 5p可通过上调ZEB1，逆转缺氧诱导的JAK/STAT和PI3K/AKT通路中磷酸化激酶的减少。我们的研究表明，抑制miR - 34a - 5p通过靶向ZEB1激活JAK/STAT和PI3K/AKT通路，从而保护心肌细胞免受缺氧诱导的细胞损伤。
Myocardial infarction (MI) is an unsolved health problem which seriously affects human health around the world. miR-34a-5p acting as a tumor-suppressor is associated with left ventricular remodeling. We aimed to explore the functional roles of miR-34a-5p in cardiomyocytes. Hypoxia-induced cell injury in H9c2, HL-1 and human cardiac myocytes was analyzed according to the decrease of cell viability and increase of apoptosis. Expression of miR-34a-5p was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) when the concentration of O-2 was decreased. Then, the effects of aberrantly expressed miR-34a-5p on proliferation and apoptosis of cardiomyocytes incubated under hypoxia were assessed. Finally, the downstream protein and signaling pathways of miR-34a-5p were explored. The hypoxic model was successfully constructed after incubation under hypoxia for 48 h. When the concentration of O-2 decreased, the miR-34a-5p level was increased significantly. Then, we found miR-34a-5p aggravated hypoxia-induced alterations of proliferation and apoptosis in cardiomyocytes. Zinc finger E-box binding homeobox 1 (ZEB1) was identified as a target of miR-34a-5p, and miR-34a-5p conferred its function via targeting ZEB1. Finally, miR-34a-5p inhibition reversed hypoxia-induced decreases of phosphorylated kinases in the JAK/STAT and PI3K/AKT pathways through up-regulating ZEB1. Our study revealed that miR-34a-5p inhibition protected cardiomyocytes against hypoxia-induced cell injury through activating the JAK/STAT and PI3K/AKT pathways by targeting ZEB1.