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长链非编码 RNA TUG1 通过下调 microRNA-127 缓解 LPS 诱导的 PC-12 细胞损伤。

Long non-coding RNA TUG1 alleviates LPS-induced injury of PC-12 cells by down-regulating microRNA-127.

机构信息

Department of Orthopedics, Ningbo No.6 Hospital, Ningbo 315040, Zhejiang, China.

Department of Orthopedics, Ningbo No.6 Hospital, Ningbo 315040, Zhejiang, China.

出版信息

Exp Mol Pathol. 2019 Oct;110:104287. doi: 10.1016/j.yexmp.2019.104287. Epub 2019 Jul 18.

Abstract

The limited therapeutic strategies and the unsatisfied prognosis for spinal cord injury (SCI) make the identification of innovative therapeutic targets for SCI become very urgent. Herein, we explored the role of long non-cording RNA taurine up-regulated gene 1 (lncRNA TUG1) in lipopolysaccharide (LPS)-treated PC-12 cells and studied the downstream effector and signaling cascades. We found that LPS-induced decrease of cell viability, increase of apoptosis and release of IL-6 and TNF-α were mitigated by TUG1 overexpression. MicroRNA (miR-127) was negatively regulated by TUG1. Effects of TUG1 on LPS-treated PC-12 cells were reversed by miR-127 overexpression. Besides, TUG1 inactivated NF-κB and p38MAPK pathways in LPS-treated PC-12 cells via down-regulating miR-127. Dynactin 4 and protein tyrosine phosphatase (PTP) were the target genes of miR-127. miR-127 regulated the NF-κB and p38MAPK pathways in PC-12 cells at least by targeting dynactin 4 and PTP. In conclusion, we discovered that TUG1 alleviated LPS-induced PC-12 cell inflammatory injury might be through down-regulating miR-127, influencing dynactin 4 and PTP, and then inactivating NF-κB and p38MAPK pathways.

摘要

有限的治疗策略和脊髓损伤(SCI)不满意的预后使得寻找创新的 SCI 治疗靶点变得非常紧迫。在此,我们研究了长链非编码 RNA 牛磺酸上调基因 1(lncRNA TUG1)在脂多糖(LPS)处理的 PC-12 细胞中的作用,并研究了下游效应物和信号级联。我们发现,TUG1 的过表达减轻了 LPS 诱导的 PC-12 细胞活力下降、细胞凋亡增加以及白细胞介素 6(IL-6)和肿瘤坏死因子-α(TNF-α)的释放。微小 RNA(miR-127)受 TUG1 负调控。miR-127 的过表达逆转了 TUG1 对 LPS 处理的 PC-12 细胞的影响。此外,TUG1 通过下调 miR-127 使 LPS 处理的 PC-12 细胞中的核因子-κB(NF-κB)和丝裂原活化蛋白激酶(p38MAPK)通路失活。动力蛋白 4(dynactin 4)和蛋白酪氨酸磷酸酶(PTP)是 miR-127 的靶基因。miR-127 通过靶向 dynactin 4 和 PTP 调节 PC-12 细胞中的 NF-κB 和 p38MAPK 通路。总之,我们发现 TUG1 减轻 LPS 诱导的 PC-12 细胞炎症损伤可能是通过下调 miR-127,影响 dynactin 4 和 PTP,从而使 NF-κB 和 p38MAPK 通路失活。

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