Bioinformatic analysis of circular RNA expression profiles in a rat lumbosacral spinal root avulsion model.

Bioinformatic analysis of circular RNA expression profiles in a rat lumbosacral spinal root avulsion model.
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大鼠腰骶椎脊髓根撕脱模型中环状RNA表达谱的生物信息学分析

DOI:
10.3389/fgene.2022.920493
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发表时间:
2022
影响因子:
3.7
通讯作者:
Zhu, Lei
Zhu, Lei
中科院分区:
生物学3区
文献类型:
--
作者:
Zhou, Zhibin;Ma, Jun;Cai, Jiao;Chen, Aimin;Zhu, Lei

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腰骶脊髓根撕脱伤(LSRA)是一种严重的神经损伤,可导致下肢毁灭性的功能障碍。据报道,环状核糖核酸(circRNAs)与多种疾病有关。然而,circrna在LSRA中的作用尚不清楚。在这里,我们进行了RNA测序(RNA-seq)来确定大鼠LSRA模型中的circRNA表达谱,并通过生物信息学分析和体外实验进一步研究了它们的潜在功能和潜在机制。共发现1708个circRNAs在LSRA后脊髓组织中差异表达(|≥2,p < 0.05),其中591个circRNAs上调,1117个circRNAs下调。同时,还发现2263个mrna存在差异表达,其中1471个mrna表达上调,792个mrna表达下调。随机选择8个circRNAs和mRNA,通过实时定量聚合酶链反应成功验证与RNA-seq结果一致。基于基因本体和《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circRNA和mRNA在LSRA中的潜在作用,circRNA/miRNA/mRNA相互作用网络显示,在LSRA中下调的circRNA circr_7025被两个神经元凋亡相关的miRNA rno-miR-1224和rno-miR-326-5p靶向。进一步的体外实验表明,circRNA_7025通过circRNA_7025/miR-1224/miR-326-5p轴保护氧糖剥夺诱导的神经元凋亡。总之,我们的研究结果揭示了circRNA表达谱及其在LSRA中的潜在功能。这些发现提高了我们对LSRA致病机制的理解,并可能使我们能够确定LSRA的新分子靶点。
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 in vitro experiments. In all, 1708 circRNAs were found to be differentially expressed in spinal cord tissues after LSRA (|fold change| ≥ 2 and p < 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 in vitro experiments revealed that circRNA_7025 protected against oxygen-glucose deprivation induced neuronal apoptosis via 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.
DOI: 10.1093/bioinformatics/btu638
发表时间: 2015-01-15
期刊: Bioinformatics (Oxford, England)
影响因子: --
作者:
Anders S;Pyl PT;Huber W
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发表时间: 2019-02-18
期刊: MOLECULAR CANCER
影响因子: 37.3
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