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lncRNA-MEG/miR-21-5p/PDCD4轴在脊髓损伤中的作用

The role of lncRNA-MEG/miR-21-5p/PDCD4 axis in spinal cord injury.

作者信息

Wang Juncheng, Zhao Yin, Tang Yifan, Li Fengning, Chen Xiongsheng

机构信息

Spine Center, Department of Orthopaedics, Shanghai Changzheng Hospital, Second Military Medical University Shanghai, China.

Department of Orthopedics, Naval Special Medical Center, Second Military Medical University Shanghai, China.

出版信息

Am J Transl Res. 2021 Feb 15;13(2):646-658. eCollection 2021.

Abstract

Spinal cord injury (SCI) is an insult to the spinal cord resulting in a change, either temporary or permanent, in its normal motor or sensory function, but the mechanism of neuron loss after spinal cord injury is still unclear. Long non-coding RNAs (lncRNAs) can play an important role in regulating cell physiological activities through competitively binding to miRNAs. However, there is still a lack of research on the effect of lncRNAs on SCI. In this study, we selected SCI gene expression data and miRNA expression data from the NCBI database for differential expression analysis, and predicted miRNA target genes. Subsequently, biological analysis of gene expression and miRNA changes was performed on a rat SCI model. The results showed that the expression level of lncRNA-MEG increased significantly in rat SCI model. Subsequently, we found that lncRNA-MEG can promote the expression level of PDCD4 by inhibiting miR-21-5p, which leads to neuronal cell apoptosis. Furthermore, knocking down of lncRNA-MEG with shRNA can reverse the effect of miR-21-5p and inhibit the effect of PDCD4 to reduce the expression of apoptosis-related proteins. Furthermore, we found lncRNA-MEG can regulate PDCD4 expression through miR-21-5p by targeting 3'UTR of PDCD4 in the OGD cell model. In summary, we first discovered lncRNA-MEG regulates neuronal cell apoptosis through miR-21-5p by targeting PDCD4 in SCI.

摘要

脊髓损伤(SCI)是对脊髓的一种损害,会导致其正常运动或感觉功能发生暂时或永久性改变,但脊髓损伤后神经元丢失的机制仍不清楚。长链非编码RNA(lncRNAs)可通过与微小RNA(miRNAs)竞争性结合,在调节细胞生理活动中发挥重要作用。然而,关于lncRNAs对脊髓损伤影响的研究仍很缺乏。在本研究中,我们从NCBI数据库中选取脊髓损伤基因表达数据和微小RNA表达数据进行差异表达分析,并预测微小RNA靶基因。随后,对大鼠脊髓损伤模型进行基因表达和微小RNA变化的生物学分析。结果显示,lncRNA-MEG在大鼠脊髓损伤模型中的表达水平显著升高。随后,我们发现lncRNA-MEG可通过抑制miR-21-5p来促进程序性细胞死亡蛋白4(PDCD4)的表达水平,从而导致神经元细胞凋亡。此外,用短发夹RNA(shRNA)敲低lncRNA-MEG可逆转miR-21-5p的作用,并抑制PDCD4的作用,以降低凋亡相关蛋白的表达。此外,我们发现在氧糖剥夺(OGD)细胞模型中,lncRNA-MEG可通过靶向PDCD4的3'非翻译区(3'UTR),经miR-21-5p调节PDCD4的表达。总之,我们首次发现lncRNA-MEG在脊髓损伤中通过靶向PDCD4,经miR-21-5p调节神经元细胞凋亡。

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