Zhou Zhibin, Ma Jun, Cai Jiao, Chen Aimin, Zhu Lei
Department of Orthopaedics, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.
Department of Orthopaedics, Naval Medical Center of PLA, Naval Medical University, Shanghai, China.
Front Genet. 2022 Aug 12;13:920493. doi: 10.3389/fgene.2022.920493. eCollection 2022.
Lumbosacral spinal root avulsion (LSRA) is a severe nerve injury that results in devastating dysfunction in the lower limb. Circular ribonucleic acids (circRNAs) have been reported to be implicated in a variety of diseases. However, the role of circRNAs in LSRA remains unclear. Here, we performed RNA sequencing (RNA-seq) to determine circRNA expression profiles in a rat LSRA model and further investigated their potential functions and the underlying mechanisms by bioinformatic analyses and experiments. In all, 1708 circRNAs were found to be differentially expressed in spinal cord tissues after LSRA (|fold change| ≥ 2 and < 0.05), with 591 up-regulated 1117 down-regulated. Meanwhile, 2263 mRNAs were also indentified to be differentially expressed, of which 1471 were upregulated and 792 were downregulated. Eight randomly selected circRNAs and mRNA were successfully verified to be consistent the RNA-seq results by quantitative real-time polymerase chain reaction. Functional analyses based on gene ontology and Kyoto Encyclopedia of Genes and Genomes predicted the potential roles of differentially expressed circRNAs and mRNAs in LSRA, and circRNA/miRNA/mRNA interaction networks revealed that circRNA_7025, a down-regulated circRNA in LSRA, was targeted by two neuronal apoptosis-related miRNAs, rno-miR-1224 and rno-miR-326-5p. Further experiments revealed that circRNA_7025 protected against oxygen-glucose deprivation induced neuronal apoptosis the circRNA_7025/miR-1224/miR-326-5p axis. In summary, our results revealed circRNA expression profiles and their potential functions in LSRA. These findings improve our understanding of the pathogenic mechanisms involved in LSRA and might enable us to identify new molecular targets for LSRA.
腰骶部脊髓神经根撕脱伤（LSRA）是一种严重的神经损伤，可导致下肢出现严重功能障碍。据报道，环状核糖核酸（circRNAs）与多种疾病有关。然而，circRNAs在LSRA中的作用仍不清楚。在此，我们进行了RNA测序（RNA-seq），以确定大鼠LSRA模型中circRNA的表达谱，并通过生物信息学分析和实验进一步研究它们的潜在功能及潜在机制。总共发现1708个circRNAs在LSRA后的脊髓组织中差异表达（|倍数变化|≥2且<0.05），其中591个上调，1117个下调。同时，还鉴定出2263个mRNA差异表达，其中1471个上调，792个下调。通过定量实时聚合酶链反应成功验证了随机选择的8个circRNAs和mRNA与RNA-seq结果一致。基于基因本体论和京都基因与基因组百科全书的功能分析预测了差异表达的circRNAs和mRNAs在LSRA中的潜在作用，circRNA/miRNA/mRNA相互作用网络显示，circRNA_7025是LSRA中一个下调的circRNA，被两个与神经元凋亡相关的miRNA，即rno-miR-1224和rno-miR-326-5p靶向。进一步的实验表明，circRNA_7025通过circRNA_7025/miR-1224/miR-326-5p轴保护神经元免受氧糖剥夺诱导的凋亡。总之，我们的结果揭示了LSRA中circRNA的表达谱及其潜在功能。这些发现增进了我们对LSRA致病机制的理解，并可能使我们能够识别出LSRA的新分子靶点。
