Differential Expression and Correlation Analysis of Global Transcriptome for Hemorrhagic Transformation After Acute Ischemic Stroke

Abstract

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.

MicroRNAs and mRNA Regulatory Network of Parenchymal Hematoma after Endovascular Mechanical Reperfusion for Acute Ischemic Stroke in Rat

“…There were 47 significantly differentially expressed microRNAs from peripheral blood in patients with HT compared with those without HT. MiRNA-383-5p was one of the top ten down-regulated microRNAs related to HT, similar to our study [21]. In the transient MCAO model of wild-type mice, miRNA-155 increased in the peri-infarct regions, which regulated BBB permeability via direct interactions with several mRNAs.…”

“…Our study provides new evidence for the association of microRNAs with PH in AIS after mechanical reperfusion therapy. Most differentially expressed microRNAs were not reported to be involved in PH after reperfusion [20,21,[36][37][38][39][40][41].…”

“…Early BBB disruption predicts HT and poor outcomes in acute stroke patients receiving EVT [16][17][18]. Non-coding RNA can contribute to cerebral ischemia-reperfusion injury and act as non-invasive biomarkers of diagnosis and prognosis for HT in patients with acute stroke [19][20][21][22]. In previous studies, we showed the preliminary results of the microRNA expression profile in rat ischemic hemispheres with HT after mechanical reperfusion using a microRNA array.…”

MicroRNA-29a-5p Attenuates Oxygen-glucose Deprivation and Reoxygenation Injury in Astrocytes by Targeting Glycogen Synthase Kinase 3β

“…Regulating microRNAs in the BBB may alleviate CIRI in animal and in vitro models with OGD/R. [8][9][10][11][12][13][14][15][16][17][18] In this study, we found microRNA-29a-5p decreased in astrocytes after OGD/R. Increased microRNA-29a-5p alleviated astrocyte injury and induced phenotype shifting of astrocytes.…”

Serum Olink Proteomics-Based Identification of Protein Biomarkers Associated with the Immune Response in Ischemic Stroke

“…PTH1R may also be associated with the risk of autism spectrum disorder . In addition, although a potential association between PTH1R or PTH1R and IS has not been investigated, the calcium-ion signaling pathway and neuroactive ligand–receptor interaction pathways have been established as key pathways in IS and post-IS hemorrhagic transformation. − Furthermore, regulating the neuroactive ligand–receptor interaction pathway also regulates ferroptosis in vascular neuronal cells, thereby affecting the occurrence and development of hypertension and IS …”