MicroRNA-494 improves functional recovery and inhibits apoptosis by modulating PTEN/AKT/mTOR pathway in rats after spinal cord injury
MicroRNA-494 improves functional recovery and inhibits apoptosis by modulating PTEN/AKT/mTOR pathway in rats after spinal cord injury
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MicroRNA-494通过调节PTEN/AKT/mTOR通路改善脊髓损伤后大鼠的功能恢复并抑制细胞凋亡
DOI：
10.1016/j.biopha.2017.05.143
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发表时间：
2017
影响因子：
7.5
通讯作者：
Che Xiaoming
中科院分区：
文献类型：
--
作者：
Zhu Huaguang;Xie Rong;Liu Xiaodong;Shou Jiajun;Gu Wentao;Gu Shixin;Che Xiaoming
挫伤脊髓损伤(SCI)的病因和治疗结果与多种细胞、分子和生化改变有关。最近的研究发现脊髓损伤后microRNAs(MiRNAs)的异常表达。然而，关于miRNAs在脊髓损伤中的独特作用的功能意义还知之甚少。在这里，我们建立了大鼠脊髓损伤模型，并应用miRNA芯片分析了脊髓损伤后不同时间miRNAs的表达。基因芯片数据显示，与假手术组相比，14个miRNAs表达上调，46个miRNAs表达下调2倍，其中miR-494下调最为显著。随后，我们对miR-494的功能进行了研究，发现agomir-494上调miR-494可以促进脊髓损伤后大鼠的功能恢复，缩小损伤范围，抑制细胞凋亡。此外，我们的数据显示miR-494通过直接靶向BV-2细胞中的3‘-UTR来抑制AKT/mTOR途径的负调控因子磷酸酶和张力蛋白同源蛋白(PTEN)。更重要的是，我们证明了miR-494的过表达通过抑制PTEN的表达而激活了AKT/mTOR信号通路。提示miR-494通过调节PTEN/AKT/mTOR通路对大鼠脊髓损伤具有保护作用，有望成为治疗脊髓损伤的候选药物。
Multiple cellular, molecular, and biochemical changes contribute to the etiology and treatment outcome of contusion spinal cord injury (SCI). MicroRNAs (miRNAs) aberrant expression have been found after SCI in recent studies. However, little is known about the functional significance of the unique role of miRNAs in SCI. Here, we established a rat SCI model and performed the miRNA microarray to analyze miRNAs expression at different times post-SCI. Microarray data revealed that 14 miRNAs were upregulated and 46 miRNAs were downregulated by 2 times compared with sham rat spinal cords, and miR-494 was one of the miRNAs being most significantly downregulated. Subsequently, we investigated miR-494 function and found that upregulation of miR-494 by agomir-494 improves functional recovery, reduces lesion size and inhibits apoptotic cell in rats following SCI. Moreover, our data showed that miR-494 suppresses phosphatase and tensin homolog (PTEN), a negative regulator of AKT/mTOR pathway, through directly targeting its 3′-UTR in BV-2 cells. Most importantly, we demonstrated that overexpression of miR-494 activates AKT/mTOR signaling pathway via inhibiting PTEN expression in rat SCI model. These findings suggested that miR-494 harbored the protective effect after SCI by modulating PTEN/AKT/mTOR pathway in rats and it is a potential candidate for SCI therapeutics.