Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Neurosurgery, Shanghai Fengxian District Central Hospital, Shanghai 201400, P.R. China.
Mol Med Rep. 2018 Aug;18(2):1504-1512. doi: 10.3892/mmr.2018.9128. Epub 2018 Jun 5.
The present study aimed to identify novel intervertebral disc degeneration (IDD)‑associated long noncoding (lnc)RNAs and genes. The lncRNA and mRNA microarray dataset GSE56081 was downloaded from the Gene Expression Omnibus database and included 5 samples from patients with degenerative lumbar nucleus pulposus and 5 normal controls. Differentially expressed lncRNAs or differentially expressed genes (DEGs) were identified and co‑expression network analysis was performed followed by functional analysis for genes in the network. Additionally, a microRNA (miRNA)‑lncRNA‑mRNA competing endogenous RNA (ceRNA) regulatory network was constructed based on DEGs and lncRNAs in the co‑expression network. Furthermore, a literature search was performed to identify specific miRNAs that had been previously associated with IDD and a specific miRNA‑associated ceRNA network was extracted from the co‑expression network. A total of 967 genes and 137 lncRNAs were differentially expressed between IDD samples and controls. A co‑expression network was constructed and contained 39 differentially expressed lncRNAs and 209 DEGs, which were primarily involved in 'skeletal system development', 'response to mechanical stimulus' and 'bone development'. Furthermore, a ceRNA network was established, including 79 miRNAs, 9 downregulated lncRNAs and 148 DEGs. The identified miRNAs included a previously reported disease‑associated miRNA, hsa‑miR‑140. The present study demonstrated that hsa‑miR‑140 was regulated by three lncRNAs in the hsa‑miR‑140‑associated ceRNA network, including KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), OIP5 antisense RNA 1 (OIP5‑AS1) and UGDH antisense RNA 1 (UGDH‑AS1). KCNQ1OT1 was co‑expressed with neurochondrin (NCDN) and lon peptidase 2, peroxisomal. In addition, the lncRNAs OIP5‑AS1 and UGDH‑AS1 targeted several overlapping co‑expressed genes, including forkhead box F1 (FOXF1) and polycystin 1, transient receptor potential channel interacting (PKD1). Therefore, KCNQ1OT1 may regulate the expression of NCDN, and OIP5‑AS1 and UGDH‑AS1 may affect the expression of FOXF1 and PKD1 in IDD. Further experiments are required to validate the results of the present study, which may provide valuable insights into the identification of novel biomarkers associated with IDD.
本研究旨在鉴定新型椎间盘退变（IDD）相关长链非编码（lnc）RNAs 和基因。从基因表达综合数据库中下载了 lncRNA 和 mRNA 微阵列数据集 GSE56081，该数据集包含 5 例退行性腰椎间盘突出症患者和 5 例正常对照的样本。鉴定差异表达的 lncRNA 或差异表达基因（DEGs），并进行共表达网络分析，随后对网络中的基因进行功能分析。此外，基于共表达网络中的 DEGs 和 lncRNAs 构建 miRNA-lncRNA-mRNA 竞争内源性 RNA（ceRNA）调控网络。进一步对文献进行检索，以鉴定先前与 IDD 相关的特定 miRNA，并从共表达网络中提取特定 miRNA 相关的 ceRNA 网络。IDD 样本与对照组之间有 967 个基因和 137 个 lncRNA 差异表达。构建了一个共表达网络，包含 39 个差异表达的 lncRNA 和 209 个 DEG，主要参与“骨骼系统发育”、“对机械刺激的反应”和“骨发育”。此外，建立了一个 ceRNA 网络，包含 79 个 miRNA、9 个下调的 lncRNA 和 148 个 DEG。鉴定的 miRNA 包括先前报道的疾病相关 miRNA，hsa-miR-140。本研究表明，hsa-miR-140 受 hsa-miR-140 相关 ceRNA 网络中 3 个 lncRNA 的调节，包括 KCNQ1 反义链/反义转录本 1（KCNQ1OT1）、OIP5 反义 RNA 1（OIP5-AS1）和 UGDH 反义 RNA 1（UGDH-AS1）。KCNQ1OT1 与神经软骨素（NCDN）和过氧化物酶体 lon 肽酶 2 共表达。此外，lncRNA OIP5-AS1 和 UGDH-AS1 靶向几个重叠的共表达基因，包括叉头框 F1（FOXF1）和多囊蛋白 1，瞬时受体电位通道相互作用（PKD1）。因此，KCNQ1OT1 可能调节 NCDN 的表达，而 OIP5-AS1 和 UGDH-AS1 可能影响 IDD 中 FOXF1 和 PKD1 的表达。需要进一步的实验来验证本研究的结果，这可能为鉴定与 IDD 相关的新型生物标志物提供有价值的见解。
