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长链非编码RNA MIR155HG通过miR-7036b-3p/GPNMB轴和AMPK/mTOR信号通路激活自噬,从而抑制脊髓损伤中的细胞凋亡。

LncRNA MIR155HG suppresses cell apoptosis by activating autophagy via miR-7036b-3p/GPNMB axis and AMPK/mTOR signaling in spinal cord injury.

作者信息

Liu Ruoxi, Ye Jintao, Huang Sihua

机构信息

Department of Orthopaedic Surgery, Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, 710004, China.

出版信息

Noncoding RNA Res. 2025 May 22;15:1-17. doi: 10.1016/j.ncrna.2025.05.013. eCollection 2025 Dec.

DOI:10.1016/j.ncrna.2025.05.013
PMID:40703249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12281537/
Abstract

BACKGROUND

Long non-coding RNAs (lncRNAs) participate in spinal cord injury (SCI) development through regulating autophagy and neuronal apoptosis. Previously, was identified as an upregulated lncRNA in rat bladder tissues harvested after SCI operation. Our study aimed to elucidate the function of in SCI.

METHODS

Glutamate (Glu)-stimulated primary mouse spinal cord neurons were used as SCI cellular models. Contusion-induced SCI mouse models were established using an improved weightlessness method. Neuronal apoptosis and autophagy affected by or silencing were assessed by TUNEL staining, flow cytometry assay, western blotting, and immunofluorescence staining. The binding of miR-7036b-3p on (or ) was verified by luciferase reporter assay. Histological changes were observed through HE and Masson staining.

RESULTS

and expression was elevated while miR-7036b-3p expression was reduced in SCI. silencing attenuated the apoptosis in Glu-stimulated neurons and ameliorated glial scar formation and motor function of SCI mice. knockdown mitigated apoptosis, enhanced autophagy, activated AMPK phosphorylation, and repressed mTOR phosphorylation. upregulated expression by sponging miR-7036b-3p. The autophagy inhibitor 3-MA reversed the above changes caused by depletion.

CONCLUSION

knockdown alleviated neuronal apoptosis by enhancing autophagy in SCI via miR-7036b-3p/ axis and AMPK/mTOR pathway.

摘要

背景

长链非编码RNA(lncRNAs)通过调节自噬和神经元凋亡参与脊髓损伤(SCI)的发展。此前,已被鉴定为脊髓损伤手术后大鼠膀胱组织中上调的lncRNA。我们的研究旨在阐明在脊髓损伤中的作用。

方法

将谷氨酸(Glu)刺激的原代小鼠脊髓神经元用作脊髓损伤的细胞模型。采用改良的失重法建立挫伤性脊髓损伤小鼠模型。通过TUNEL染色、流式细胞术检测、蛋白质印迹法和免疫荧光染色评估受或沉默影响的神经元凋亡和自噬。通过荧光素酶报告基因检测验证miR-7036b-3p与(或)的结合。通过苏木精-伊红(HE)和Masson染色观察组织学变化。

结果

在脊髓损伤中,和的表达升高,而miR-7036b-3p的表达降低。沉默可减轻Glu刺激的神经元中的细胞凋亡,并改善脊髓损伤小鼠的胶质瘢痕形成和运动功能。敲低可减轻细胞凋亡,增强自噬,激活AMPK磷酸化,并抑制mTOR磷酸化。通过海绵吸附miR-7036b-3p上调的表达。自噬抑制剂3-MA可逆转耗竭引起的上述变化。

结论

敲低通过miR-7036b-3p/轴和AMPK/mTOR途径增强脊髓损伤中的自噬,从而减轻神经元凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d43/12281537/f89b8eb7d9b6/gr11.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d43/12281537/a2f3fd4bbc46/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d43/12281537/625f610308df/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d43/12281537/d7cd393509f8/gr2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d43/12281537/b1598b31facf/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d43/12281537/1a0ec706102f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d43/12281537/2471d965d39a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d43/12281537/15b737044454/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d43/12281537/d122a821a2aa/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d43/12281537/f7f1890681b1/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d43/12281537/6a4865489542/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d43/12281537/f89b8eb7d9b6/gr11.jpg

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