基于全转录组数据揭示黄韧带骨化过程中与代谢相关的新基因

IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine Pub Date : 2024-07-15 DOI:10.1002/jsp2.1357
Yongzhao Zhao, Qian Xiang, Shuai Jiang, Jialiang Lin, Weishi Li
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引用次数: 0

摘要

背景:黄韧带骨化(OLF)是胸椎脊髓病的主要原因之一。以往的研究表明,代谢紊乱与黄韧带骨化症的发病机制之间可能存在潜在联系。本研究旨在通过严格的代谢相关基因生物信息学工作流程和实验验证,确定代谢紊乱在OLF发病机制中的潜在作用:方法:基于代谢相关基因的一系列生物信息学方法,利用单样本基因组富集分析比较了OLF组织和正常黄韧带(LF)组织的代谢得分。通过基因本体富集分析、京都基因和基因组百科全书富集分析以及蛋白-蛋白相互作用等方法,筛选出了与OLF相关和与代谢相关的差异表达基因(OMDEGs),并探讨了OMDEGs的生物学功能。根据成对的 miRNA 中枢 OMDEGs 构建了竞争性内源性 RNA(ceRNA)网络。进行了相关性分析,以探讨 OLF 代谢紊乱与免疫异常之间的潜在关系。最后,通过细胞实验验证了GBE1和TNF-α在LF细胞成骨分化中的作用:结果:OLF组织与正常LF组织的代谢评分存在明显差异。筛选出49个OMDEGs,并确定了它们的生物学功能。建立了包含三个中心 OMDEGs 和五个差异表达 miRNAs(DEmiRNAs)的 ceRNA 网络。中枢 OMDEG 与 OLF 相关浸润免疫细胞之间的相关性分析表明,代谢紊乱可能通过改变 LF 组织的局部免疫状态而导致 OLF。细胞实验确定了 GBE1 表达和 TNF-α 在 LF 细胞成骨分化中的重要作用:该研究首次通过严格的生物信息学算法和实验验证,初步阐明了代谢紊乱在OLF发病机制中的重要作用,为今后研究OLF的发病机制和筛选有效的治疗靶点提供了新的思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Revealing the novel metabolism-related genes in the ossification of the ligamentum flavum based on whole transcriptomic data

Revealing the novel metabolism-related genes in the ossification of the ligamentum flavum based on whole transcriptomic data

Backgrounds

The ossification of the ligamentum flavum (OLF) is one of the major causes of thoracic myelopathy. Previous studies indicated there might be a potential link between metabolic disorder and pathogenesis of OLF. The aim of this study was to determine the potential role of metabolic disorder in the pathogenesis of OLF using the strict bioinformatic workflow for metabolism-related genes and experimental validation.

Methods

A series of bioinformatic approaches based on metabolism-related genes were conducted to compare the metabolism score between OLF tissues and normal ligamentum flavum (LF) tissues using the single sample gene set enrichment analysis. The OLF-related and metabolism-related differentially expressed genes (OMDEGs) were screened out, and the biological functions of OMDEGs were explored, including the Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and protein–protein interaction. The competing endogenous RNA (ceRNA) network based on pairs of miRNA-hub OMDEGs was constructed. The correlation analysis was conducted to explore the potential relationship between metabolic disorder and immunity abnormality in OLF. In the end, the cell experiments were performed to validate the roles of GBE1 and TNF-α in the osteogenic differentiation of LF cells.

Results

There was a significant difference of metabolism score between OLF tissues and normal LF tissues. Forty-nine OMDEGs were screened out and their biological functions were determined. The ceRNA network containing three hub OMDEGs and five differentially expressed miRNAs (DEmiRNAs) was built. The correlation analysis between hub OMDEGs and OLF-related infiltrating immune cells indicated that metabolic disorder might contribute to the OLF via altering the local immune status of LF tissues. The cell experiments determined the important roles of GBE1 expression and TNF-α in the osteogenic differentiation of LF cells.

Conclusions

This research, for the first time, preliminarily illustrated the vital role of metabolic disorder in the pathogenesis of OLF using strict bioinformatic algorithms and experimental validation for metabolism-related genes, which could provide new insights for investigating disease mechanism and screening effective therapeutic targets of OLF in the future.

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来源期刊
JOR Spine
JOR Spine ORTHOPEDICS-
CiteScore
6.40
自引率
18.90%
发文量
42
审稿时长
10 weeks
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