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

Background: Long non-coding RNAs (lncRNAs) participate in spinal cord injury (SCI) development through regulating autophagy and neuronal apoptosis. Previously, MIR155HG was identified as an upregulated lncRNA in rat bladder tissues harvested after SCI operation. Our study aimed to elucidate the func...

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Main Authors: Ruoxi Liu, Jintao Ye, Sihua Huang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-12-01
Series:Non-coding RNA Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468054025000678
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author Ruoxi Liu
Jintao Ye
Sihua Huang
author_facet Ruoxi Liu
Jintao Ye
Sihua Huang
author_sort Ruoxi Liu
collection DOAJ
description Background: Long non-coding RNAs (lncRNAs) participate in spinal cord injury (SCI) development through regulating autophagy and neuronal apoptosis. Previously, MIR155HG was identified as an upregulated lncRNA in rat bladder tissues harvested after SCI operation. Our study aimed to elucidate the function of MIR155HG 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 MIR155HG or GPNMB silencing were assessed by TUNEL staining, flow cytometry assay, western blotting, and immunofluorescence staining. The binding of miR-7036b-3p on MIR155HG (or GPNMB) was verified by luciferase reporter assay. Histological changes were observed through HE and Masson staining. Results: MIR155HG and GPNMB expression was elevated while miR-7036b-3p expression was reduced in SCI. MIR155HG silencing attenuated the apoptosis in Glu-stimulated neurons and ameliorated glial scar formation and motor function of SCI mice. GPNMB knockdown mitigated apoptosis, enhanced autophagy, activated AMPK phosphorylation, and repressed mTOR phosphorylation. MIR155HG upregulated GPNMB expression by sponging miR-7036b-3p. The autophagy inhibitor 3-MA reversed the above changes caused by GPNMB depletion. Conclusion: MIR155HG knockdown alleviated neuronal apoptosis by enhancing autophagy in SCI via miR-7036b-3p/GPNMB axis and AMPK/mTOR pathway.
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spelling doaj-art-e3279950fd584f45a09be0c4c8702ba72025-08-20T02:39:16ZengKeAi Communications Co., Ltd.Non-coding RNA Research2468-05402025-12-011511710.1016/j.ncrna.2025.05.013LncRNA MIR155HG suppresses cell apoptosis by activating autophagy via miR-7036b-3p/GPNMB axis and AMPK/mTOR signaling in spinal cord injuryRuoxi Liu0Jintao Ye1Sihua Huang2Department of Orthopaedic Surgery, Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, 710004, ChinaDepartment of Orthopaedic Surgery, Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, 710004, ChinaCorresponding author. Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, No.157, Xiwu Road, Xincheng District, Xi 'an City, Shaanxi Province, China.; Department of Orthopaedic Surgery, Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, 710004, ChinaBackground: Long non-coding RNAs (lncRNAs) participate in spinal cord injury (SCI) development through regulating autophagy and neuronal apoptosis. Previously, MIR155HG was identified as an upregulated lncRNA in rat bladder tissues harvested after SCI operation. Our study aimed to elucidate the function of MIR155HG 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 MIR155HG or GPNMB silencing were assessed by TUNEL staining, flow cytometry assay, western blotting, and immunofluorescence staining. The binding of miR-7036b-3p on MIR155HG (or GPNMB) was verified by luciferase reporter assay. Histological changes were observed through HE and Masson staining. Results: MIR155HG and GPNMB expression was elevated while miR-7036b-3p expression was reduced in SCI. MIR155HG silencing attenuated the apoptosis in Glu-stimulated neurons and ameliorated glial scar formation and motor function of SCI mice. GPNMB knockdown mitigated apoptosis, enhanced autophagy, activated AMPK phosphorylation, and repressed mTOR phosphorylation. MIR155HG upregulated GPNMB expression by sponging miR-7036b-3p. The autophagy inhibitor 3-MA reversed the above changes caused by GPNMB depletion. Conclusion: MIR155HG knockdown alleviated neuronal apoptosis by enhancing autophagy in SCI via miR-7036b-3p/GPNMB axis and AMPK/mTOR pathway.http://www.sciencedirect.com/science/article/pii/S2468054025000678Spinal cord injuryMIR155HGGPNMBAMPK/mTORApoptosisAutophagy
spellingShingle Ruoxi Liu
Jintao Ye
Sihua Huang
LncRNA MIR155HG suppresses cell apoptosis by activating autophagy via miR-7036b-3p/GPNMB axis and AMPK/mTOR signaling in spinal cord injury
Non-coding RNA Research
Spinal cord injury
MIR155HG
GPNMB
AMPK/mTOR
Apoptosis
Autophagy
title LncRNA MIR155HG suppresses cell apoptosis by activating autophagy via miR-7036b-3p/GPNMB axis and AMPK/mTOR signaling in spinal cord injury
title_full LncRNA MIR155HG suppresses cell apoptosis by activating autophagy via miR-7036b-3p/GPNMB axis and AMPK/mTOR signaling in spinal cord injury
title_fullStr LncRNA MIR155HG suppresses cell apoptosis by activating autophagy via miR-7036b-3p/GPNMB axis and AMPK/mTOR signaling in spinal cord injury
title_full_unstemmed LncRNA MIR155HG suppresses cell apoptosis by activating autophagy via miR-7036b-3p/GPNMB axis and AMPK/mTOR signaling in spinal cord injury
title_short LncRNA MIR155HG suppresses cell apoptosis by activating autophagy via miR-7036b-3p/GPNMB axis and AMPK/mTOR signaling in spinal cord injury
title_sort lncrna mir155hg suppresses cell apoptosis by activating autophagy via mir 7036b 3p gpnmb axis and ampk mtor signaling in spinal cord injury
topic Spinal cord injury
MIR155HG
GPNMB
AMPK/mTOR
Apoptosis
Autophagy
url http://www.sciencedirect.com/science/article/pii/S2468054025000678
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