Department of Biopharmaceutical Sciences (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, P. O. Box 19, Harbin, 150081, Heilongjiang, China.
Sci Rep. 2021 Jun 2;11(1):11584. doi: 10.1038/s41598-021-91059-9.
Circular RNA (circRNA), a novel class of noncoding RNAs, has been used extensively to complement transcriptome remodeling in the central nervous system, although the genomic coverage provided has rarely been studied in intracerebral hemorrhage (ICH) and is limited and fails to provide a detailed picture of the cerebral transcriptome landscape. Here, we described sequencing-based transcriptome profiling, providing comprehensive analysis of cerebral circRNA, messenger RNA (mRNA) and microRNA (miRNA) expression in ICH rats. In the study, male Sprague-Dawley rats were subjected to ICH, and next-generation sequencing of RNAs isolated from non-hemorrhagic (Sham) and hemorrhagic (ICH) rat brain samples collected 7 (early phase) and 28 (chronic phase) days after insults, was conducted. Bioinformatics analysis was performed to determine miRNA binding sites and gene ontology of circRNAs, target genes of miRNAs, as well as biological functions of mRNAs, altered after ICH. These analyses revealed different expression profiles of circRNAs, mRNAs and miRNAs in day-7 and day-28 ICH groups, respectively, compared with the Sham. In addition, the expression signature of circRNAs was more sensitive to disease progression than that of mRNAs or miRNAs. Further analysis suggested two temporally specific circRNA-miRNA-mRNA networks based on the competitive endogenous RNA theory, which had profound impacts on brain activities after ICH. In summary, these results suggested an important role for circRNAs in the pathogenesis of ICH and in reverse remodeling based on self-protection support, providing deep insights into diverse possibilities for ICH therapy through targeting circRNAs.
环状 RNA（circRNA）作为一类新型非编码 RNA，已被广泛用于补充中枢神经系统转录组重构，尽管在脑出血（ICH）中很少研究其提供的基因组覆盖范围，且该研究具有局限性，无法提供大脑转录组景观的详细描述。在这里，我们描述了基于测序的转录组分析，为 ICH 大鼠的脑 circRNA、信使 RNA（mRNA）和 microRNA（miRNA）表达提供了全面的分析。在这项研究中，雄性 Sprague-Dawley 大鼠接受 ICH 造模，对非出血（Sham）和出血（ICH）大鼠脑样本中分离的 RNA 进行了新一代测序，这些样本分别采集于损伤后 7（早期）和 28（慢性）天。通过生物信息学分析，确定了 circRNA、miRNA 的靶基因和 mRNAs 的结合位点及基因本体，这些基因在 ICH 后发生改变。这些分析分别显示了在 day-7 和 day-28 ICH 组与 Sham 相比，circRNAs、mRNAs 和 miRNAs 的不同表达谱。此外，circRNA 的表达特征比 mRNAs 或 miRNAs 对疾病进展更敏感。进一步的分析表明，基于竞争内源性 RNA 理论，有两个具有时间特异性的 circRNA-miRNA-mRNA 网络，它们对 ICH 后的大脑活动有深远的影响。总之，这些结果表明 circRNAs 在 ICH 的发病机制和基于自我保护支持的反向重构中起重要作用，为通过靶向 circRNAs 为 ICH 治疗提供了深入的见解。
