Circular RNA expression profiles alter significantly after intracerebral hemorrhage in rats
Circular RNA expression profiles alter significantly after intracerebral hemorrhage in rats
复制标题
大鼠脑出血后，环状 RNA 表达谱发生显着变化。
DOI：
10.1016/j.brainres.2019.146490
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发表时间：
2020-01-01
期刊：
影响因子：
2.9
通讯作者：
Chen, Gao
中科院分区：
文献类型：
--
作者：
Dou, Zhangqi;Yu, Qian;Chen, Gao
环状rna （circRNAs）是一类共价封闭的非编码rna，其表达模式的异常改变在许多疾病中被研究。本研究旨在探讨脑出血（ICH）是否影响大鼠脑中的circRNA表达谱。以成年雄性Sprague-Dawley大鼠为研究对象，采用体腔内注射自体动脉血建立脑出血模型。收集血肿周围的大脑皮层，于6 h、12 h和24 h进行circRNA芯片检测。采用定量逆转录pcr （qRT-PCR）验证结果。应用生物信息学方法预测ceRNA网络，并对三个时间点的亲本基因和靶mrna进行富集分析。与假手术组相比，脑出血后6 h、12 h和24 h大鼠大脑皮层中分别有111、1145、1751个circrna上调，47、732、1329个circrna下调。大多数来自外显子区。三个时间点上调93例，下调20例。通过qRT-PCR确认3个circRNAs的芯片结果。亲本基因的GO和KEGG分析显示，从6小时的蛋白质复合物组装、细胞间粘附和cAMP信号通路，到12小时和24小时的细胞内信号转导、蛋白质磷酸化和谷氨酸能突触的转变。成功预测了circRNA-miRNA-mRNA网络。靶向mrna富集分析表明，Rap1、Ras、MAPK、PI3K-Akt、TNF和Wnt信号通路在肿瘤中的转录调控和通路。这是第一个证明脑出血显著改变环状rna表达的研究，具有治疗干预的希望靶点。
Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs, and aberrant alteration of their expression patterns is studied in numerous diseases. This study aimed to investigate whether intracerebral hemorrhage (ICH) affected circRNA expression profiles in the rat brain. Adult male Sprague-Dawley rats were subjected to intrastriatal injection of autologous artery blood to establish the ICH model. The cerebral cortex around hematoma was collected to perform circRNA microarray at 6 h, 12 h and 24 h. Quantitative reverse transcription-PCR (qRT-PCR) was used to validate the results. Bioinforrnatic methods were applied to predict ceRNA network and perform enrichment analyses for parent genes at three time points and target mRNAs. 111, 1145, 1751 up-regulated and 47, 732, 1329 down-regulated circRNAs were detected in the cerebral cortex of rats at 6 h, 12 h and 24 h after ICH compared with sham group. Most were from exonic regions. 93 were up-regulated and 20 were down-regulated at all three time points. Microarray results of 3 circRNAs were confirmed via qRT-PCR. GO and KEGG analyses for parent genes showed transition from protein complex assembly, cell-cell adhesion and cAMP signaling pathway at 6 h to intracellular signal transduction, protein phosphorylation and glutamatergic synapse at 12 h and 24 h. A circRNA-miRNA-mRNA network was successfully predicted. Enrichment analyses of targeted mRNAs indicated transcriptional regulations and pathways including Rap1, Ras, MAPK, PI3K-Akt, TNF and Wnt signaling and pathways in cancer. This was the first study to demonstrate that ICH significantly altered the expression of circRNAs with promising targets for therapeutic intervention.