Low back pain influences people of every age and is one of the major contributors to the global cost of illness. Intervertebral disc degeneration (IVDD) is a major contributor to low back pain, but its pathogenesis is unknown. Recently, ferroptosis has been shown to have a substantial role in modulating IVDD progression. However, the function of ferroptosis-related long non-coding RNAs (lncRNAs) has rarely been reported in IVDD. Consequently, the research was conducted to explore the ferroptosis-related lncRNA signature in the IVDD occurrence and development. We analyzed two datasets (GSE167199 and GSE167931) archived in the NCBI Gene Expression Omnibus (GEO) public database. We screened differentially expressed genes (DEGs) and differentially expressed lncRNAs (DELncs) in these datasets using the limma package. Ferroptosis-related genes (FRGs) were derived from the FerrDb V2 website and the intersection of DEGs and FRGs was considered as differentially expressed ferroptosis-related genes (DFGs). These genes were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Correlations between DFGs and DELncs were shown by Pearson test to determine differential expression of ferroptosis-related lncRNAs. The Pearson test showed that CPEB1-HTR2A-AS1 and ACSL3-DNAJC27-AS1 pairs had correlation coefficients over 0.9. Twenty ferroptosis-related lncRNAs were identified and validated in IVDD. Eight of these lncRNAs were upregulated in IVDD nucleus pulposus cells, including HTR2A-AS1, MIF-AS1, SLC8A1-AS1, LINC00942, DUXAP8, LINC00161, LUCAT1 and LINC01615. Twelve were downregulated in IVDD nucleus pulposus cells, including DNAJC27-AS1, H19, LINC01588, LINC02015, FLNC1, CARMN, PRKG1-AS1, APCDD1L-DT, LINC00839, LINC00536, LINC00710 and LINC01535. Eighteen of the 20 lncRNAs (excluding H19 and LUCAT1) were identified as ferroptosis-related lncRNAs for the first time and verified in IVDD. We have identified a ferroptosis-related lncRNA signature involved in IVDD and revealed a close relationship between CPEB1 and HTR2A-AS1, and between ACSL3 and DNAJC27-AS1. Our findings indicate that ferroptosis-related lncRNAs are a new target set for the early detection and therapy of IVDD.

中文翻译：

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椎间盘退变中铁死亡相关 lncRNA 特征的鉴定和验证

腰痛影响各个年龄段的人，是造成全球疾病成本的主要原因之一。椎间盘退变（IVDD）是腰痛的主要原因，但其发病机制尚不清楚。最近，铁死亡已被证明在调节 IVDD 进展中具有重要作用。然而，铁死亡相关的长非编码RNA（lncRNA）的功能在IVDD中却鲜有报道。因此，本研究旨在探讨 IVDD 发生和发展中与铁死亡相关的 lncRNA 特征。我们分析了 NCBI 基因表达综合 (GEO) 公共数据库中存档的两个数据集（GSE167199 和 GSE167931）。我们使用 limma 包筛选了这些数据集中的差异表达基因 (DEG) 和差异表达 lncRNA (DELncs)。铁死亡相关基因（FRG）源自 FerrDb V2 网站，DEG 和 FRG 的交叉点被认为是差异表达的铁死亡相关基因（DFG）。然后对这些基因进行基因本体论和京都基因和基因组百科全书分析。通过 Pearson 检验显示 DFG 和 DELnc 之间的相关性，以确定铁死亡相关 lncRNA 的差异表达。 Pearson检验显示CPEB1-HTR2A-AS1和ACSL3-DNAJC27-AS1对的相关系数超过0.9。在 IVDD 中鉴定并验证了 20 种与铁死亡相关的 lncRNA。其中 8 个 lncRNA 在 IVDD 髓核细胞中上调，包括 HTR2A-AS1、MIF-AS1、SLC8A1-AS1、LINC00942、DUXAP8、LINC00161、LUCAT1 和 LINC01615。 IVDD 髓核细胞中有 12 个表达下调，包括 DNAJC27-AS1、H19、LINC01588、LINC02015、FLNC1、CARMN、PRKG1-AS1、APCDD1L-DT、LINC00839、LINC00536、LINC00710 和 LINC01535。 20个lncRNA中的18个（不包括H19和LUCAT1）首次被鉴定为铁死亡相关lncRNA，并在IVDD中得到验证。我们鉴定了 IVDD 中涉及的铁死亡相关 lncRNA 特征，并揭示了 CPEB1 和 HTR2A-AS1 之间以及 ACSL3 和 DNAJC27-AS1 之间的密切关系。我们的研究结果表明，铁死亡相关的 lncRNA 是 IVDD 早期检测和治疗的新靶点。