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miR-2954抑制心肌硒缺乏中的PI3K信号传导并诱导自噬和凋亡。

miR-2954 Inhibits PI3K Signaling and Induces Autophagy and Apoptosis in Myocardium Selenium Deficiency.

作者信息

Liu Qi, Cai Jingzeng, Gao Yunan, Yang Jie, Gong Yafan, Zhang Ziwei

机构信息

College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Cell Physiol Biochem. 2018;51(2):778-792. doi: 10.1159/000495332. Epub 2018 Nov 21.

Abstract

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.

摘要

背景/目的:硒(Se)缺乏可导致多种心脏疾病,包括人类的克山病、猪的桑椹心疾病和鸡的心脏损伤。微小RNA近年来一直是研究热点,并已被证明参与细胞死亡自噬这一新途径,其在多种类型的心脏病中可发挥重要作用。

方法

微小RNA组分析显示,缺硒鸡心肌中miR - 2954表达增加,且预测PI3K为其靶基因。通过双荧光素酶检测以及RNA蛋白质相互作用预测和分子对接软件验证了miR - 2954与PI3K之间的靶标关系。采用qRT - PCR和蛋白质免疫印迹法检测缺硒鸡以及miR - 2954基因敲除/过表达心肌细胞中PI3K及相关信号通路成分的表达。

结果

在本研究中,我们观察到miR - 2954过表达在体内外均导致PI3K信号通路受到抑制。

结论

缺硒心肌中miR - 2954表达增加,而miR - 2954过表达通过调控PI3K信号通路,在心脏损伤时导致心肌细胞自噬和凋亡;这种现象是机体的自我保护机制还是由miR - 2954造成的损伤,有待进一步研究。我们的研究结果为心肌细胞凋亡提供了新的见解;此外,旨在为心肌病的诊断和靶向治疗提供新方向。

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