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Long Non-Coding RNA MALAT1 Protects Against Spinal Cord Injury via Suppressing microRNA-125b-5p Mediated Microglial M1 Polarization, Neuroinflammation, and Neural Apoptosis

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Abstract

Our previous studies have discovered that long non-coding RNA (lncRNA) MALAT1 and its target microRNA-125b-5p (miR-125b-5p) are implicated in neurological diseases via regulating neuroinflammation and neuronal injury. This study aimed to further explore the relationship between lncRNA MALAT1 and miR-125b-5p, as well as their effect on microglial activation, neuroinflammation, and neural apoptosis in spinal cord injury (SCI). Primary microglia from Sprague Dawley rats were stimulated with lipopolysaccharide (LPS). Then, microglia were transfected with lncRNA MALAT1 overexpression or knock-down adenovirus-associated virus with or without miR-125b-5p mimic. The culture medium of microglia was incubated with primary neurons. SCI rats were established for in vivo validation. LncRNA MALAT1 expression was reduced by LPS treatment in a dose-dependent manner. LncRNA MALAT1 overexpression suppressed the microglial M1 polarization (decreased iNOS but increased ARG1), neuroinflammation (declined PTGS2, TNF-α, IL-1β, and IL-6), and microglia-induced neural apoptosis (lower TUNEL positive cells and C-caspase3 but higher BCL2) under LPS treatment; its knock-down displayed the opposite trend. Moreover, lncRNA MALAT1 directly bound to and negatively regulated miR-125b-5p. MiR-125b-5p mimic promoted microglial M1 polarization, neuroinflammation, and microglia-induced neural apoptosis following LPS treatment; also, it could attenuate the effect of lncRNA MALAT1. Further in vivo study displayed that lncRNA MALAT1 overexpression elevated the Basso-Beattie-Bresnahan motor function score and improved neural injury. Also, in vivo validation indicated a similar effect of lncRNA MALAT1 on microglial polarization and neuroinflammation as in vitro. LncRNA MALAT1 improves SCI recovery via miR-125b-5p mediated microglial M1 polarization, neuroinflammation, and neural apoptosis.

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Data Availability

The datasets generated during and/or analysed during the current study may be attained from the corresponding author upon reasonable request.

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Funding

This study was supported by Beijing Medical and Health Foundation (No. B17773) and The 23456 Talent Project of Henan Provincial People’s Hospital.

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Authors and Affiliations

  1. Department of Pharmacy, Henan Provincial People’s Hospital, Zhengzhou, 450000, Henan, China

    Yuanlong Li, Jun Sun, Ming Ni, Fengqin Fang, Wei Zhang & Peizhi Ma

  2. Department of Pharmacy, People’s Hospital of Zhengzhou University, Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, 450000, Henan, China

    Yuanlong Li, Jun Sun, Fengqin Fang, Wei Zhang & Peizhi Ma

  3. Department of Pharmacy, People’s Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, 450000, Henan, China

    Yuanlong Li, Jun Sun, Fengqin Fang, Wei Zhang & Peizhi Ma

  4. School of Clinical Medicine, The First Affiliated Hospital of Henan University of Science and Technology, Henan University of Science and Technology, Luoyang, 471003, Henan, China

    Hua Fan

  5. Department of Neurology, Henan Provincial People’s Hospital, Zhengzhou, 450000, Henan, China

    Xiong Han

  6. Department of Clinical Pharmacy, Fuwai Central China Cardiovascular Hospital, Zhengzhou, 450000, Henan, China

    Ming Ni

  7. Ward of Heart Failure, Fuwai Central China Cardiovascular Hospital, Zhengzhou, 450000, Henan, China

    Xiaodan Hou

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  1. Yuanlong Li
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Contributions

All authors designed and conceived the study. YLL, HF, XH, JS and MN participated in the experiments and data collection. YLL, HF, XDH, FQF, and WZ performed the data analysis. YLL, HF, and XH wrote the manuscript. JS, MN, XDH, FQF, WZ and PZM contributed to results analysis and revised the manuscript. All authors confirmed the authenticity of all the raw data. All authors read and approved the final manuscript.

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Correspondence to Peizhi Ma.

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The experiment protocol was approved by the Animal Care and Use Committee and referred to National Institutes of Health guidelines.

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Li, Y., Fan, H., Han, X. et al. Long Non-Coding RNA MALAT1 Protects Against Spinal Cord Injury via Suppressing microRNA-125b-5p Mediated Microglial M1 Polarization, Neuroinflammation, and Neural Apoptosis. Mol Neurobiol 61, 2136–2150 (2024). https://doi.org/10.1007/s12035-023-03664-6

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