Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Front Immunol. 2021 Nov 9;12:765382. doi: 10.3389/fimmu.2021.765382. eCollection 2021.
Oxidative stress (OS) irreversibly affects the pathogenesis of intervertebral disc degeneration (IDD). Certain non-coding RNAs act as competitive endogenous RNAs (ceRNAs) that regulate IDD progression. Analyzing the signatures of oxidative stress-related gene (OSRG) pairs and regulatory ceRNA mechanisms and immune-infiltration patterns associated with IDD may enable researchers to distinguish IDD and reveal the underlying mechanisms. In this study, OSRGs were downloaded and identified using the Gene Expression Omnibus database. Functional-enrichment analysis revealed the involvement of oxidative stress-related pathways and processes, and a ceRNA network was generated. Differentially expressed oxidative stress-related genes (De-OSRGs) were used to construct De-OSRG pairs, which were screened, and candidate De-OSRG pairs were identified. Immune cell-related gene pairs were selected immune-infiltration analysis. A potential long non-coding RNA-microRNA-mRNA axis was determined, and clinical values were assessed. Eighteen De-OSRGs were identified that were primarily related to intricate signal-transduction pathways, apoptosis-related biological processes, and multiple kinase-related molecular functions. A ceRNA network consisting of 653 long non-coding RNA-microRNA links and 42 mRNA-miRNA links was constructed. Three candidate De-OSRG pairs were screened out from 13 De-OSRG pairs. The abundances of resting memory CD4 T cells, resting dendritic cells, and CD8 T cells differed between the control and IDD groups. CD8 T cell infiltration correlated negatively with cyclin B1 () expression and positively with protein kinase D1 () expression. - was the only pair that was differentially expressed in IDD, was correlated with CD8 T cells, and displayed better predictive accuracy compared to individual genes. The -- and -- axes may regulate IDD. Our findings indicate that the OSRG pair -, which regulates oxidative stress during IDD development, is a robust signature for identifying IDD. This OSRG pair and increased infiltration of CD8 T cells, which play important roles in IDD, were functionally associated. Thus, the OSRG pair - is promising target for treating IDD.
氧化应激（OS）不可逆转地影响椎间盘退变（IDD）的发病机制。某些非编码 RNA 作为竞争性内源性 RNA（ceRNA），调节 IDD 的进展。分析与 IDD 相关的氧化应激相关基因（OSRG）对和调节 ceRNA 机制以及免疫浸润模式的特征，可能使研究人员能够区分 IDD 并揭示潜在机制。在这项研究中，使用基因表达综合数据库下载和鉴定 OSRGs。功能富集分析显示氧化应激相关途径和过程的参与，并生成 ceRNA 网络。差异表达的氧化应激相关基因（De-OSRGs）用于构建 De-OSRG 对，筛选候选 De-OSRG 对。选择免疫细胞相关基因对进行免疫浸润分析。确定了潜在的长非编码 RNA-miRNA-mRNA 轴，并评估了临床价值。鉴定出 18 个主要与复杂信号转导途径、凋亡相关生物过程和多种激酶相关分子功能相关的 De-OSRG。构建了包含 653 个长非编码 RNA-miRNA 链接和 42 个 mRNA-miRNA 链接的 ceRNA 网络。从 13 个 De-OSRG 对中筛选出 3 对候选 De-OSRG 对。对照组和 IDD 组之间静止记忆 CD4 T 细胞、静止树突状细胞和 CD8 T 细胞的丰度不同。CD8 T 细胞浸润与 cyclin B1（）表达呈负相关，与蛋白激酶 D1（）表达呈正相关。是唯一在 IDD 中差异表达的基因对，与 CD8 T 细胞相关，并且与单个基因相比显示出更好的预测准确性。-和--轴可能调节 IDD。我们的研究结果表明，在 IDD 发展过程中调节氧化应激的 OSRG 对--是识别 IDD 的稳健特征。该 OSRG 对与在 IDD 中起重要作用的 CD8 T 细胞浸润增加具有功能相关性。因此，OSRG 对--是治疗 IDD 的有前途的靶点。
