Circular RNA Expression Alteration and Bioinformatics Analysis in Rats After Traumatic Spinal Cord Injury
Circular RNA Expression Alteration and Bioinformatics Analysis in Rats After Traumatic Spinal Cord Injury
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脊髓外伤后大鼠环状 RNA 表达变化及生物信息学分析
DOI：
10.3389/fnmol.2018.00497
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发表时间：
2019-01-14
影响因子：
4.8
通讯作者：
Li, Jian-Jun
中科院分区：
文献类型：
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作者：
Qin, Chuan;Liu, Chang-Bin;Li, Jian-Jun
脊髓损伤（SCI）主要是由外伤引起的。由于原发性机械损伤在 SCI 中是不可避免的，因此有必要关注 SCI 引起的继发性损伤的病理生理学和潜在分子机制，为 SCI 患者开发有前景的治疗方法。环状RNA（circRNA）与多种疾病相关。然而，迄今为止的研究尚未确定 circRNA 在创伤性 SCI 中的功能作用。我们使用微阵列和定量逆转录 PCR (qRT-PCR) 检查了大鼠挫伤脊髓中的 circRNA 表达谱，然后利用生物信息学预测了它们在 SCI 后病理生理学中的潜在作用。我们使用 circRNA 微阵列在挫伤后 3 天的脊髓中发现总共 1676 个差异表达的 circRNA（倍数变化 >= 2.0；P < 0.05）； 1261 个 circRNA 显着下调，而其余 415 个 circRNA 显着上调。然后，经qRT-PCR验证后，5个选定的circRNA，即rno_circRNA_005342、rno_circRNA_015513、rno_circRNA_002948、rno_circRNA_006096和rno_circRNA_013017在SCI组中均显着下调，在微阵列和PCR数据中显示出相似的表达模式。该研究的下一部分涉及使用生物信息学分析预测 circRNA/miRNA/mRNA 相互作用。在研究的最后部分，基因本体论（GO）和京都基因与基因组百科全书分析表明碳水化合物代谢过程是GO分析后最重要的富集和最有意义的术语之一，受circRNAs-miRNAs轴影响的前两条信号通路是AMP激活的蛋白激酶信号通路和过氧化物酶体相关通路。总之，这项研究显示了 circRNA 表达模式的改变，可能参与了创伤性 SCI 后大鼠的生理和病理过程，为通过调节 circRNA 来深入了解 SCI 治疗靶点的多种可能性提供了深入的见解。
Spinal cord injury (SCI) is mostly caused by trauma. As primary mechanical injury is unavoidable in SCI, a focus on the pathophysiology and underlying molecular mechanisms of SCI-induced secondary injury is necessary to develop promising treatments for SCI patients. Circular RNAs (circRNAs) are associated with various diseases. Nevertheless, studies to date have not yet determined the functional roles of circRNAs in traumatic SCI. We examined circRNA expression profiles in the contused spinal cords of rats using microarray and quantitative reverse transcription-PCR (qRT-PCR) then predict their potential roles in post-SCI pathophysiology with bioinformatics. We found a total of 1676 differentially expressed circRNAs (fold change >= 2.0; P < 0.05) in spinal cord 3 days after contusion using circRNA microarray; 1261 circRNAs were significantly downregulated, whereas the remaining 415 were significantly upregulated. Then, five selected circRNAs, namely, rno_circRNA_005342, rno_circRNA_015513, rno_circRNA_002948, rno_circRNA_006096, and rno_circRNA_013017 were all significantly downregulated in the SCI group after verification by qRT-PCR, demonstrating a similar expression pattern in both microarray and PCR data. The next section of the study was concerned with the prediction of circRNA/miRNA/mRNA interactions using bioinformatics analysis. In the final part of the study, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses indicated carbohydrate metabolic process was one of the most significant enrichments and meaningful terms after GO analysis, and the top two signaling pathways affected by the circRNAs-miRNAs axes were the AMP-activated protein kinase signaling pathway and the peroxisome related pathway. In summary, this study showed an altered circRNA expression pattern that may be involved in physiological and pathological processes in rats after traumatic SCI, providing deep insights into numerous possibilities for SCI treatment targets by regulating circRNAs.