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长链非编码RNA H19和HOTAIR与椎间盘退变有关。

Long Non-Coding RNAs H19 and HOTAIR Implicated in Intervertebral Disc Degeneration.

作者信息

Wang Zhun, Zhang Jingwei, Zheng Wei, He Yongjin

机构信息

Department of Pain, Tianjin First Central Hospital, Tianjin, China.

出版信息

Front Genet. 2022 Mar 3;13:843599. doi: 10.3389/fgene.2022.843599. eCollection 2022.

Abstract

Intervertebral disc degeneration (IDD) is the major cause of low back pain. We aimed to identify the key genes for IDD pathogenesis. An integrated analysis of microarray datasets of IDD archived in public Gene Expression Omnibus was performed. Bioinformatics analyses including identification of differentially expressed mRNAs/microRNAs/long non-coding RNAs (DEMs/DEMis/DELs), pathway enrichment, and competitive endogenous RNA (ceRNA) network construction were performed to give insights into the potential functions of differentially expressed genes (DEGs, including DEMs, DEMis, and DELs). The diagnostic value of DEMis in distinguishing IDD from normal controls was evaluated through receiver operating characteristic (ROC) analysis. DEGs were identified in IDD, including H19 and HOTAIR. In the DEMis-DEMs network of IDD, miR-1291, miR-4270, and miR-320b had high connectivity with targeted DEMs. Cell death biological processes and the JAK-STAT pathway were significantly enriched from targeted DEMs. The area under the curve (AUC) of 10 DEMs including miR-1273e, miR-623, miR-518b, and miR-1291 in ROC analysis was more than 0.8, which indicated that those 10 DEMs had diagnostic value in distinguishing IDD from normal individuals. DELs H19 and HOTAIR were related to IDD pathogenesis. Cell death biological processes and the JAK-STAT pathway might play key roles in IDD development.

摘要

椎间盘退变(IDD)是腰痛的主要原因。我们旨在确定IDD发病机制的关键基因。对公共基因表达综合数据库中存档的IDD微阵列数据集进行了综合分析。进行了生物信息学分析,包括差异表达的mRNA/微小RNA/长链非编码RNA(DEM/DEMi/DEL)的鉴定、通路富集分析以及竞争性内源性RNA(ceRNA)网络构建,以深入了解差异表达基因(DEG,包括DEM、DEMi和DEL)的潜在功能。通过受试者工作特征(ROC)分析评估了DEMi在区分IDD与正常对照中的诊断价值。在IDD中鉴定出了DEG,包括H19和HOTAIR。在IDD的DEMi-DEM网络中,miR-1291、miR-4270和miR-320b与靶向DEM具有高度连接性。细胞死亡生物学过程和JAK-STAT通路在靶向DEM中显著富集。包括miR-1273e、miR-623、miR-518b和miR-1291在内的10个DEMi在ROC分析中的曲线下面积(AUC)大于0.8,这表明这10个DEMi在区分IDD与正常个体方面具有诊断价值。DEL H19和HOTAIR与IDD发病机制相关。细胞死亡生物学过程和JAK-STAT通路可能在IDD发展中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48da/8927764/1ee696c54c1e/fgene-13-843599-g001.jpg

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