• Jianwei Chen, Xiaosheng Yu, Manle Qiu, Fan Feng, Zude Liu, and Guibin Zhong.
• Department of Spine Surgery, Department of Orthopedics, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
• Spine. 2021 Sep 1; 46 (17): E916-E925.

Study DesignSequencing and experimental analysis of the expression profile of circular RNAs (circRNAs) in hypertrophic ligamentum flavum (LFH).ObjectivesThe 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 DataHypertrophy 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.MethodsA 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.ResultsThe 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.ConclusionThis 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.Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

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