Zhong Yulan, Li Xiaoqiang, Li Chuqiao, Li Yudi, He Yuqi, Li Fangming, Ling Li
Department of Neurology, Shenzhen Hospital, Southern Medical University Shenzhen, Guangdong, China.
Department of Neurology, The First Affiliated Hospital, Jinan University Guangzhou, Guangdong, China.
Am J Transl Res. 2020 Aug 15;12(8):4160-4174. eCollection 2020.
Circular RNAs (circRNAs), formed from pre-messenger RNAs by back-splicing, are a novel class of evolutionarily-conserved endogenous non-coding RNAs. While circRNAs are involved in various diseases, the role of circRNAs in intracerebral hemorrhage (ICH) remains unknown. In the present study, we performed high-throughput sequencing to profile the expression of circRNAs in the rat brain at 24 and 48 hours after ICH onset, and utilized bioinformatics methods to make predictions about the function of dysregulated circRNAs. Compared with the sham group, 346 and 389 circRNAs changed significantly (|log2 (fold change)| > 1 and < 0.05) at 24 and 48 hours after ICH, respectively. Bioinformatics analyses indicated that parent genes of dysregulated circRNAs were involved in biological processes, cellular component, and molecular function following ICH, and that they were enriched in the dopaminergic synapses, glutamatergic synapses, endocytosis, regulation of actin cytoskeleton, the mitogen-activated protein kinase signaling pathway, and the retrograde endocannabinoid signaling pathway. Enrichment analyses of target mRNAs showed that these mRNAs were enriched in synaptic plasticity, ion channel activity, and pathways including the phospholipase D signaling and the cGMP-PKG signaling. Our study indicates that the expression profile of circRNAs changes significantly after ICH in rat brains, and suggests that circRNAs may be crucial for the pathophysiological process following ICH.
环状RNA(circRNAs)由前体信使RNA通过反向剪接形成,是一类新型的进化保守的内源性非编码RNA。虽然circRNAs参与多种疾病,但circRNAs在脑出血(ICH)中的作用仍不清楚。在本研究中,我们进行了高通量测序以分析ICH发作后24小时和48小时大鼠脑中circRNAs的表达,并利用生物信息学方法预测失调circRNAs的功能。与假手术组相比,ICH后24小时和48小时分别有346个和389个circRNAs发生显著变化(|log2(倍数变化)|>1且<0.05)。生物信息学分析表明,失调circRNAs的亲本基因在ICH后参与生物过程、细胞成分和分子功能,并且它们在多巴胺能突触、谷氨酸能突触、内吞作用、肌动蛋白细胞骨架调节、丝裂原活化蛋白激酶信号通路和逆行内源性大麻素信号通路中富集。对靶mRNA的富集分析表明,这些mRNA在突触可塑性、离子通道活性以及包括磷脂酶D信号传导和cGMP-PKG信号传导在内的途径中富集。我们的研究表明,大鼠脑ICH后circRNAs的表达谱发生显著变化,并提示circRNAs可能对ICH后的病理生理过程至关重要。