miR-2954 Inhibits PI3K Signaling and Induces Autophagy and Apoptosis in Myocardium Selenium Deficiency
miR-2954 Inhibits PI3K Signaling and Induces Autophagy and Apoptosis in Myocardium Selenium Deficiency
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miR-2954 抑制缺硒心肌中的 PI3K 信号传导并诱导自噬和细胞凋亡
DOI：
10.1159/000495332
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Zhang, Ziwei
中科院分区：
文献类型：
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作者：
Liu, Qi;Cai, Jingzeng;Zhang, Ziwei
背景/目的：硒缺乏可导致多种心脏疾病，包括人的克山病、猪的桑葚心病和鸡的心脏损伤。MicroRNA是近年来的研究热点，已被证明参与细胞死亡的新途径-自噬，在几种类型的心脏病中发挥重要作用。研究方法：MicroRNAome分析显示，miR-2954在缺硒鸡心肌组织中的表达增加，推测PI 3 K为靶基因。通过双荧光酶法和RNA蛋白相互作用预测及分子对接软件验证miR-2954与PI 3 K的靶向关系。采用qRT-PCR和western blotting检测硒缺乏鸡和miR-2954敲除/过表达心肌细胞中PI 3 K及相关通路组分的表达。结果如下：在本研究中，我们观察到miR-2954过表达导致体内PI 3 K通路的抑制，并且在体外导致体内和体外PI 3 K通路的抑制。结论：miR-2954在缺硒心肌中表达增加，而miR-2954过表达通过调节PI 3 K通路导致心肌细胞在心肌损伤过程中发生自噬和凋亡，这一现象是机体的自我保护机制还是miR-2954造成的损伤还需要进一步研究。我们的发现为心肌细胞凋亡提供了新的见解;此外，我们的目标是为心肌疾病的诊断和靶向治疗提供新的方向。
Background/Aims: Selenium (Se) deficiency can lead to several cardiac diseases, including Keshan disease in humans, mulberry heart disease in pigs and cardiac injury in chickens. MicroRNAs have been a research focus in recent years and have been shown to participate in a new avenue of cell death-autophagy, which can play a significant role in several types of heart disease. Methods: MicroRNAome analysis showed that the expression of miR-2954 was increased in the myocardium of selenium-deficient chickens, and PI3K was predicted to be the target gene. The target relationship between miR-2954 and PI3K was verified with a double fluorescence enzyme assay and RNA Protein Interaction Prediction and molecular docking software. qRT-PCR and western blotting were used to detect the expression of PI3K and related pathway components in selenium-deficient chickens and miR-2954 knockout/overexpression cardiomyocytes. Results: In this study, we observed that miR-2954 overexpression led to inhibition of PI3K pathway in vivo and in vitroled to inhibition of the PI3K pathway in vivo and in vitro. Conclusion: The expression of miR-2954 was increased in selenium-deficient myocardium, whereas overexpression of miR-2954 led to autophagy and apoptosis of myocardial cells during cardiac injury through regulation of the PI3K pathway; whether this phenomenon is a self-protection mechanism of the organism or damage caused by miR-2954 requires further study. Our findings provides new insight apoptosis in cardiomyocytes; additionally, we aim to provide a new direction for the diagnosis and targeted treatment of myocardial diseases.