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Stat3 诱导的长链非编码 RNA Kcnq1ot1 调控脊髓损伤中神经元细胞的凋亡。

Stat3-Induced lncRNA Kcnq1ot1 Regulates the Apoptosis of Neuronal Cells in Spinal Cord Injury.

机构信息

Department of Neurosurgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.

Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China.

出版信息

J Mol Neurosci. 2022 Mar;72(3):610-617. doi: 10.1007/s12031-021-01932-5. Epub 2021 Nov 3.

Abstract

Emerging evidence validates the vital roles of long noncoding RNAs (lncRNAs) in spinal cord injury (SCI), which attracts great attention. In the present study, our study investigated the function and in-depth mechanism of lncRNA Kcnq1 overlapping transcript 1 (Kcnq1ot1) in SCI. Results indicated that lncRNA Kcnq1ot1 expression upregulated in the hypoxia-administered neuronal cells (PC12 cells) and SCI rat models. Moreover, transcription factor signal transducer and activator of transcription 3 (Stat3) accelerated the transcriptional enrichment of Kcnq1ot1 in SCI cellular model. Functional experiments demonstrated that Kcnq1ot1 knockdown repressed the apoptosis of neuronal cells. Mechanistically, Kcnq1ot1 recruited EZH2 to the promoter region of p27 to repress its transcription. Taken together, our results indicate that Stat3-induced lncRNA Kcnq1ot1 regulates the apoptosis in SCI through epigenetically silencing p27, contributing to novel therapeutic target for SCI.

摘要

越来越多的证据证实长非编码 RNA(lncRNA)在脊髓损伤(SCI)中起着重要作用,引起了广泛关注。在本研究中,我们研究了 lncRNA Kcnq1 重叠转录本 1(Kcnq1ot1)在 SCI 中的功能和深入机制。结果表明,lncRNA Kcnq1ot1 在缺氧处理的神经元细胞(PC12 细胞)和 SCI 大鼠模型中表达上调。此外,转录因子信号转导和转录激活因子 3(Stat3)加速了 Kcnq1ot1 在 SCI 细胞模型中的转录富集。功能实验表明,Kcnq1ot1 敲低抑制了神经元细胞的凋亡。机制上,Kcnq1ot1 将 EZH2 募集到 p27 的启动子区域,从而抑制其转录。总之,我们的结果表明,Stat3 诱导的 lncRNA Kcnq1ot1 通过表观遗传沉默 p27 来调节 SCI 中的细胞凋亡,为 SCI 的治疗提供了新的靶点。

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