环状 RNA 表达谱在腰椎管狭窄症伴肥厚黄韧带患者中的研究。
Circular RNA Expression Profile in Patients with Lumbar Spinal Stenosis Associated with Hypertrophied Ligamentum Flavum.
机构信息
Department of Spine Surgery, Department of Orthopedics, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Medical Department, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
出版信息
Spine (Phila Pa 1976). 2021 Sep 1;46(17):E916-E925. doi: 10.1097/BRS.0000000000003975.
STUDY DESIGN
Sequencing and experimental analysis of the expression profile of circular RNAs (circRNAs) in hypertrophic ligamentum flavum (LFH).
OBJECTIVES
The aim of this study was to identify differentially expressed circRNAs between LFH and nonhypertrophic ligamentum flavum tissues from lumbar spinal stenosis (LSS) patients.
SUMMARY OF BACKGROUND DATA
Hypertrophy of the ligamentum flavum (LF) can cause LSS. circRNAs are important in various diseases. However, no circRNA expression patterns related to LF hypertrophy have been reported.
METHODS
A total of 33 patients with LSS participated in this study. LF tissue samples were obtained when patients underwent decompressive laminectomy during surgery. The expression profile of circRNAs was analyzed by transcriptome high-throughput sequencing and validated with quantitative real-time polymerase chain reaction (PCR). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed for the differentially expressed circRNA-associated genes and related pathways. The connections between circRNAs and microRNAs were explored using Cytoscape. The role of hsa_circ_0052318 on LF cell fibrosis was assessed by analyzing the expression of collagen I and collagen III.
RESULTS
The results showed that 2439 circRNAs of 4025 were differentially expressed between the LFH and nonhypertrophic ligamentum flavum tissues, including 1276 upregulated and 1163 downregulated circRNAs. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these differentially expressed circRNAs functioned in biological processes, cellular components, and molecular functions. Autophagy and mammalian target of rapamycin were the top two signaling pathways affected by these circRNAs. Five circRNAs (hsa_circ_0021604, hsa_circ_0025489, hsa_circ_0002599, hsa_circ_0052318, and hsa_circ_0003609) were confirmed by quantitative real-time PCR. The network indicated a strong relationship between circRNAs and miRNAs. Furthermore, hsa_circ_0052318 overexpression decreased mRNA and protein expression of collagen I and III in LF cells from LFH tissues.
CONCLUSION
This study identified circRNA expression profiles characteristic of hypertrophied LF in LSS patients, and demonstrated that hsa_circ_0052318 may play an important role in the pathogenesis of LF hypertrophy.Level of Evidence: N/A.
研究设计
对腰椎管狭窄症（LSS）患者肥厚黄韧带（LFH）中的环状 RNA（circRNA）表达谱进行测序和实验分析。
目的
本研究旨在鉴定 LFH 与非肥厚黄韧带组织之间差异表达的 circRNAs。
背景资料概要
黄韧带肥厚（LFH）可引起 LSS。circRNAs 在各种疾病中具有重要作用。然而，尚未有与 LF 肥厚相关的 circRNA 表达模式的报道。
方法
共有 33 例 LSS 患者参与了本研究。当患者在手术中接受减压椎板切除术时，从患者获取 LF 组织样本。通过转录组高通量测序分析 circRNAs 的表达谱，并通过定量实时聚合酶链反应（PCR）进行验证。对差异表达的 circRNA 相关基因及其相关通路进行基因本体论和京都基因与基因组百科全书分析。使用 Cytoscape 探索 circRNAs 与 microRNAs 之间的关系。通过分析胶原 I 和胶原 III 的表达来评估 hsa_circ_0052318 对 LF 细胞纤维化的作用。
结果
结果显示，在 LFH 和非肥厚黄韧带组织之间，有 2439 个 circRNAs 存在差异表达，其中 1276 个上调，1163 个下调。基因本体论和京都基因与基因组百科全书分析表明，这些差异表达的 circRNAs 在生物过程、细胞成分和分子功能中发挥作用。自噬和哺乳动物雷帕霉素靶蛋白是受这些 circRNAs 影响的两个主要信号通路。通过定量实时 PCR 验证了 5 个 circRNAs（hsa_circ_0021604、hsa_circ_0025489、hsa_circ_0002599、hsa_circ_0052318 和 hsa_circ_0003609）。该网络表明 circRNAs 与 miRNAs 之间存在很强的关系。此外，hsa_circ_0052318 的过表达降低了来自 LFH 组织的 LF 细胞中胶原 I 和 III 的 mRNA 和蛋白表达。
结论
本研究鉴定了 LSS 患者肥厚 LF 特有的 circRNA 表达谱，并表明 hsa_circ_0052318 可能在 LF 肥厚的发病机制中发挥重要作用。
证据水平
无。
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