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高压氧治疗促进脊髓损伤恢复:长链非编码RNA分析

Hyperbaric Oxygen Treatment in Spinal Cord Injury Recovery: Profiling Long Noncoding RNAs.

作者信息

Liu Xuehua, Liang Fang, Sun Zhencheng, Yang Jing, Su Qingjun

机构信息

Department of Hyperbaric Oxygen, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

出版信息

Spine (Phila Pa 1976). 2023 Feb 1;48(3):213-222. doi: 10.1097/BRS.0000000000004525. Epub 2022 Nov 3.

DOI:10.1097/BRS.0000000000004525
PMID:36607628
Abstract

STUDY DESIGN

A functional, transcriptome, and long noncoding RNAs (lncRNAs) expression analysis in the spinal cord of mice after hyperbaric oxygen (HBO) treatment.

OBJECTIVE

We aimed to explore the mechanism by which HBO treats spinal cord injury (SCI) at the level of lncRNAs.

SUMMARY OF BACKGROUND DATA

Immense amounts of research have established that HBO treatment promotes the recovery of neurological function after SCI. The mechanism of action remains to be clarified.

METHODS

High-throughput RNA sequencing, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were used to profile lncRNA expression and analyze biological function in the spinal cords of mice from sham-operated, SCI, and HBO-treated groups. The differential expression of lncRNA between the groups was assessed using real-time quantitative polymerase chain reaction.

RESULTS

Differential expression across 577 lncRNAs was identified among the three groups. GO analysis showed that free ubiquitin chain polymerization, ubiquitin homeostasis, DNA replication, synthesis of RNA primer, single-stranded telomeric DNA binding, and alpha-amylase activity were significantly enriched. Kyoto Encyclopedia of Genes and Genomes enrichment analysis displayed that vitamin B6 metabolism, one carbon pool by folate, DNA replication, lysine degradation, beta-alanine metabolism, fanconi anemia pathway, and Notch signal pathway were the main pathways with enrichment significance. LncRNAs NONMMUT 092674.1, NONMMUT042986.2, and NONMMUT018850.2 showed significantly different expression between the SCI and the other two groups (P<0.05, <0.01).

CONCLUSIONS

This study is the first to determine the expression profiles of lncRNAs in the injured spinal cord after HBO treatment. We identified several important dysregulated lncRNAs in this setting. These results help us better understand the mechanism by which HBO treats SCI and provide new potential therapeutic targets for SCI.

摘要

研究设计

对高压氧(HBO)治疗后小鼠脊髓进行功能、转录组及长链非编码RNA(lncRNA)表达分析。

目的

我们旨在探讨HBO在lncRNA水平治疗脊髓损伤(SCI)的机制。

背景数据总结

大量研究已证实HBO治疗可促进SCI后神经功能恢复。其作用机制仍有待阐明。

方法

采用高通量RNA测序、基因本体论及京都基因与基因组百科全书富集分析,对假手术组、SCI组和HBO治疗组小鼠脊髓中的lncRNA表达进行分析并评估其生物学功能。采用实时定量聚合酶链反应评估各组间lncRNA的差异表达。

结果

三组间共鉴定出577个lncRNA存在差异表达。基因本体论分析显示,游离泛素链聚合、泛素稳态、DNA复制、RNA引物合成、单链端粒DNA结合及α-淀粉酶活性显著富集。京都基因与基因组百科全书富集分析表明,维生素B6代谢、叶酸一碳池、DNA复制、赖氨酸降解、β-丙氨酸代谢、范可尼贫血通路及Notch信号通路是具有富集意义的主要通路。lncRNAs NONMMUT 092674.1、NONMMUT042986.2和NONMMUT018850.2在SCI组与其他两组之间表现出显著差异表达(P<0.05,<0.01)。

结论

本研究首次确定了HBO治疗后损伤脊髓中lncRNA的表达谱。我们在这种情况下鉴定出了几种重要的失调lncRNA。这些结果有助于我们更好地理解HBO治疗SCI的机制,并为SCI提供新的潜在治疗靶点。

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