Han Rongrong, Zhang Peng, Li Hongfang, Chen Yun, Hao Yongnan, Guo Qiang, Zhang Aimei, Li Daojing
Department of Clinical Medicine, Jining Medical University, Jining, China.
Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, China.
Front Neurosci. 2022 Jun 8;16:889689. doi: 10.3389/fnins.2022.889689. eCollection 2022.
In order to explore the epigenetic characteristics of hemorrhagic transformation (HT) after acute ischemic stroke, we used transcriptome sequencing technology to analyze the global transcriptome expression profile of patients with and without HT after acute ischemic stroke and to study the differential expression of messenger RNA (mRNA), long noncoding RNA (lncRNA), circular RNA (circRNA) and mircoRNA (miRNA) between the two groups. To further explore the role of differentially expressed genes in HT, we annotated the function of differentially expressed genes by using gene ontology (GO) and pathway analysis on the results and showed that there were 1,051 differential expressions of lncRNAs, 2,575 differential expressions of mRNAs, 447 differential expressions of circRNAs and 47 miRNAs in patients with HT compared with non-HT patients. Pathway analysis showed that ubiquitin-mediated proteolysis, MAPK signal pathway, axon guidance, HIF-1 signal pathway, NOD-like receptor signal pathway, beta-alanine metabolism, Wnt signal pathway, sphingolipid signal pathway, neuroactive ligand-receptor interaction, and intestinal immune network used in IgA production play an important role in HT. Terms such as iron homeostasis, defense response, immune system process, DNA conformational change, production of transforming growth factor beta-2, and oxidoreductase activity were enriched in the gene list, suggesting a potential correlation with HT. A total of 261 lncRNA-miRNA relationship pairs and 21 circRNA-miRNA relationship pairs were obtained; additionally, 5 circRNAs and 13 lncRNAs were screened, which can be used as competing endogenous RNA (ceRNA) to compete with miRNA in the co-expression network. Co-expression network analysis shows that these differentially expressed circRNA and lncRNA may play a vital role in HT and provide valuable information for new biomarkers or therapeutic targets.
为了探究急性缺血性卒中后出血转化(HT)的表观遗传特征,我们运用转录组测序技术分析急性缺血性卒中后发生和未发生HT患者的整体转录组表达谱,并研究两组之间信使核糖核酸(mRNA)、长链非编码核糖核酸(lncRNA)、环状核糖核酸(circRNA)和微小核糖核酸(miRNA)的差异表达。为进一步探究差异表达基因在HT中的作用,我们对结果运用基因本体论(GO)和通路分析对差异表达基因的功能进行注释,结果显示,与未发生HT的患者相比,发生HT的患者中有1051个lncRNA差异表达、2575个mRNA差异表达、447个circRNA差异表达和47个miRNA差异表达。通路分析表明,泛素介导的蛋白水解、丝裂原活化蛋白激酶(MAPK)信号通路、轴突导向、缺氧诱导因子-1(HIF-1)信号通路、核苷酸结合寡聚化结构域样受体信号通路、β-丙氨酸代谢、Wnt信号通路、鞘脂信号通路、神经活性配体-受体相互作用以及参与免疫球蛋白A(IgA)产生的肠道免疫网络在HT中起重要作用。铁稳态、防御反应、免疫系统过程、DNA构象变化、转化生长因子β-2的产生以及氧化还原酶活性等术语在基因列表中富集,提示与HT可能存在相关性。共获得261对lncRNA-miRNA关系对和21对circRNA-miRNA关系对;此外,筛选出5个circRNA和13个lncRNA,它们可作为竞争性内源RNA(ceRNA)在共表达网络中与miRNA竞争。共表达网络分析表明,这些差异表达的circRNA和lncRNA可能在HT中起关键作用,并为新的生物标志物或治疗靶点提供有价值的信息。