Qin Chuan, Liu Chang-Bin, Yang De-Gang, Gao Feng, Zhang Xin, Zhang Chao, Du Liang-Jie, Yang Ming-Liang, Li Jian-Jun
School of Rehabilitation Medicine, Capital Medical University, Beijing, China.
China Rehabilitation Science Institute, Beijing, China.
Front Mol Neurosci. 2019 Jan 14;11:497. doi: 10.3389/fnmol.2018.00497. eCollection 2018.
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; < 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.
脊髓损伤(SCI)大多由外伤引起。由于原发性机械损伤在脊髓损伤中不可避免,因此关注脊髓损伤诱导的继发性损伤的病理生理学及潜在分子机制对于开发针对脊髓损伤患者的有效治疗方法至关重要。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在创伤性脊髓损伤中的功能作用。我们使用微阵列和定量逆转录聚合酶链反应(qRT-PCR)检测大鼠脊髓挫伤后circRNA的表达谱,然后通过生物信息学预测它们在脊髓损伤后病理生理学中的潜在作用。我们使用circRNA微阵列发现,挫伤后3天脊髓中共有1676个差异表达的circRNA(倍数变化≥2.0;P<0.05);1261个circRNA显著下调,其余415个显著上调。然后,经qRT-PCR验证,五个选定的circRNA,即rno_circRNA_005342、rno_circRNA_015513、rno_circRNA_002948、rno_circRNA_## 006096和rno_circRNA_013017在脊髓损伤组中均显著下调,在微阵列和PCR数据中显示出相似的表达模式。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分析后最显著的富集和有意义的术语之一,受circRNAs-miRNAs轴影响的前两个信号通路是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,本研究显示了circRNA表达模式的改变,这可能参与创伤性脊髓损伤后大鼠的生理和病理过程,为通过调节circRNAs治疗脊髓损伤的众多可能性提供了深入见解。