构建基于环状 RNA 的竞争性内源性 RNA 网络筛选与椎间盘退变相关的生物标志物。
Construction of a circular RNA-based competing endogenous RNA network to screen biomarkers related to intervertebral disc degeneration.
机构信息
Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University, 150 Jimo Road, Shanghai, 200092, China.
Department of Surgery of Spine and Spinal Cord, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, 450003, Henan, China.
出版信息
BMC Musculoskelet Disord. 2022 Jul 15;23(1):675. doi: 10.1186/s12891-022-05579-0.
BACKGROUND
Intervertebral disc degeneration (IDD) is a leading cause of disability with limited treatment strategies. A better understanding of the mechanism of IDD might enable less invasive and more targeted treatments. This study aimed to identify the circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) regulatory mechanisms in IDD. METHODS : The GSE67567 microarray dataset was downloaded from the Gene Expression Omnibus database. After data preprocessing, differentially expressed circRNAs, miRNAs and mRNAs between IDD and controls were identified. A ceRNA network was constructed on the basis of the interaction between circRNAs and miRNAs, and miRNAs and mRNAs. Pathway enrichment analysis was performed on the mRNAs in the ceRNA network. Then, with 'intervertebral disc degeneration' as keywords, IDD-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were searched for in the Comparative Toxicogenomics Database.
RESULTS
A total of 105 differentially expressed circRNAs, 84 miRNAs and 967 mRNAs were identified. After analysis, 86 circRNA-miRNA, and 126 miRNA-mRNA regulatory relationship pairs were obtained to construct a ceRNA network. The mRNAs were enriched in six KEGG signalling pathways, and four were associated with IDD: the hsa04350: TGF-beta signalling pathway, hsa04068: FoxO signalling pathway, hsa05142: Chagas disease (American trypanosomiasis) and hsa04380: Osteoclast differentiation. An IDD-related ceRNA network was constructed involving four circRNAs, three miRNAs and 11 mRNAs. Auxiliary validation showed that the expression levels of miR-185-5p, miR-486-5p, ACVR1B, FOXO1, SMAD2 and TGFB1 were consistent in different databases.
CONCLUSIONS
Our study identified some circRNA-miRNA-mRNA interaction axes potentially associated with the progression of IDD, viz.: circRNA_100086-miR-509-3p-MAPK1, circRNA_000200-miR-185-5p-TGFB1, circRNA_104308-miR-185-5p-TGFB1, circRNA_400090-miR-486-5p-FOXO1 and circRNA_400090-miR-486-5p-SMAD2.
背景
椎间盘退变（IDD）是导致残疾的主要原因，治疗策略有限。更好地了解 IDD 的发病机制可能会使治疗方法变得更少侵入性和更具针对性。本研究旨在鉴定 IDD 中的环状 RNA（circRNA）-微小 RNA（miRNA）-信使 RNA（mRNA）竞争性内源 RNA（ceRNA）调控机制。
方法
从基因表达综合数据库中下载 GSE67567 微阵列数据集。在数据预处理后，鉴定出 IDD 与对照组之间差异表达的 circRNA、miRNA 和 mRNA。基于 circRNA 和 miRNA 以及 miRNA 和 mRNA 之间的相互作用构建 ceRNA 网络。对 ceRNA 网络中的 mRNA 进行通路富集分析。然后，以“椎间盘退变”为关键词，在比较毒理学基因组数据库中搜索与 IDD 相关的京都基因与基因组百科全书（KEGG）通路。
结果
共鉴定出 105 个差异表达的 circRNA、84 个 miRNA 和 967 个 mRNA。分析后，获得了 86 个 circRNA-miRNA 和 126 个 miRNA-mRNA 调控关系对，构建了 ceRNA 网络。这些 mRNAs 富集在 6 个 KEGG 信号通路中，其中 4 个与 IDD 相关：hsa04350：TGF-β信号通路、hsa04068：FoxO 信号通路、hsa05142：恰加斯病（美洲锥虫病）和 hsa04380：破骨细胞分化。构建了一个与 IDD 相关的 ceRNA 网络，涉及四个 circRNA、三个 miRNA 和 11 个 mRNA。辅助验证显示，不同数据库中 miR-185-5p、miR-486-5p、ACVR1B、FOXO1、SMAD2 和 TGFB1 的表达水平一致。
结论
本研究鉴定了一些与 IDD 进展相关的 circRNA-miRNA-mRNA 相互作用轴，即：circRNA_100086-miR-509-3p-MAPK1、circRNA_000200-miR-185-5p-TGFB1、circRNA_104308-miR-185-5p-TGFB1、circRNA_400090-miR-486-5p-FOXO1 和 circRNA_400090-miR-486-5p-SMAD2。
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