Characteristics And Functional Prediction Of Plasma Exosome-derived CircRNA In Patients With Acute Intracerebral Hemorrhage

Research purpose:Intracerebral hemorrhage(ICH)is one of the main causes of death and disability in China’s population.At present,the effective treatment for ICH patients is very limited.The mechanism of secondary brain injury,nerve regeneration and repair after ICH has been the focus of research for a long time.Hypertension is the main cause of ICH,but its mechanism in ICH is still unclear.The expression and function of non-coding RNA(nc RNAs)were significantly changed after ICH.There were many subtypes of non-coding RNA(nc RNAs),among which mi RNA,lnc RNA,circRNA and other subtypes were closely related to ICH model.Previous studies have shown that circRNA is widely involved in the physiological and pathological processes of the nervous system and can stably exist in cerebrospinal fluid through the blood-brain barrier.CircRNA can directly affect the development of the nervous system and regulate the proliferation,differentiation and apoptosis of nerve cells.At present,the role of circRNA in ICH patients is not clear.This study,through high-throughput sequencing and bioinformatics analysis,analyzes the differential expression of circRNA in plasma secretion after ICH,predicts its biological function and mechanism of action,and preliminarily explores the potential of circRNA as a biomarker for ICH diagnosis,and may also serve as a target for therapeutic intervention.Research methods:In this study,six ICH patients and six healthy patients were selected from peripheral venous blood to isolate plasma exocrine body.After extracting the exocrine body RNA,Sure Print G3 Human ce RNA chip and Agilent Feature Extraction were used to detect and extract the exocrine body circRNA and m RNA.Compare and analyze the differentially expressed circRNA in the exocrine of ICH patients and healthy controls,and analyze their host/target genes through GO and KEGG analysis.According to Spearman correlation analysis,the GCS score,bleeding volume and circRNA signal value of ICH patients were analyzed by rank correlation,and the top10 circRNAs with large correlation coefficient were selected.CircRNA-binding mi RNAs were screened by mi Randa and Target Scan.Target Scan and RNAiter were used to predict mi RNA target m RNA.The selected 10 circRNAs and their corresponding mi RNAs and m RNA were used to construct circRNA-mi RNA-m RNA network through Cytascape 3.9.1.The type and location of RNA binding protein (RBP)binding to differentially expressed circRNA were predicted by circinteractome.The probability of differential expression of circRNA encoded protein was estimated by circ Bank,and the analysis of coding probability was> 0.99 circRNA.Research results:The results of high-throughput sequencing showed that there were 96 circRNAs significantly up-regulated and 353 significantly down-regulated in the ICH group compared with the control group.The differentially expressed circRNAs host gene is mainly involved in the process of ubiquitination of protein and the process of mitochondrial autophagy inflammation,which affects the occurrence of ICH.According to circRNA-mi RNA-m RNA network and target gene GO and KEGG analysis,: hsa＿circ＿00054843 sponge adsorption mi R-3610-3P regulates NEDD4 L,participates in Na+reabsorption,regulates osmotic pressure,and aggravates brain edema reaction after inflammation;hsa＿circ＿0010493 sponge adsorption mi R-23b-5p regulates the expression of E2F2,participates in the process of vascular endothelial aging,and induces the occurrence of ICH;hsa＿circ＿00090516 inhibits ROHA by adsorbing mi R-1227-5P,affects the transformation of microglia,and aggravates the inflammatory reaction after ICH.EIF4A3 in RBP has the potential to bind with a large number of functional RNA molecules.The deletion of EIF4A3 leads to the increase of autophagy and lysosome,which leads to the increase of autophagy.The loss of Hu R may lead to the dysfunction of vascular smooth muscle cell contraction,cause hypertension,and further progress leads to ICH.Conclusion:(1)There was a significant difference between the patients with intracerebral hemorrhage and the control group in plasma exosome-derived circRNA.(2)This study predicts: hsa＿circ＿00054843 sponge mi R＿3610-3P regulates the expression of NEDD4 L,participates in the reabsorption of Na+,regulates osmotic pressure,and aggravates the brain edema reaction after inflammation;hsa＿circ＿0010493 sponge adsorption mi R-23b-5p regulates the expression of E2F2,participates in the process of vascular endothelial aging,and causes ICH;hsa＿circ＿00090516 inhibits ROHA by adsorbing mi R-1227-5P,affects the transformation of microglia,and aggravates the inflammatory reaction after ICH;These pathways may affect the occurrence and development of intracerebral hemorrhage,which provides ideas for further elucidating the pathogenesis of ICH and exploring new biomarker(3)CircRNA may participate in ICH process through RBP,including eukaryotic transcription initiation factor(EIF4A3)and HUR protein(HUR).