Circular RNAs Expression Profiles In Brain Tissue Of Neonatal Rat With White Matter Damage

Objectives:To explore the expression profile of circ RNAs in neonatal rats brain with white matter damage(WMD),and investigating the potential role of these circ RNAs in the pathological process of WMD.The aim is to provide a new idea for seeking a molecular marker and molecular target for diagnosing and therapy to preterm infant white matter damage.Methods:Sprague-Dawley rats(P3 rats)were used to establish the rat model of WMD.24 hours after the model was established,the animals were sacrificed.After RNA extraction,reverse transcription,then high-throughput RNA sequencing technology was used to screen the differential expression of circ RNAs in brain tissue of rats with WMD group and Sham control.At the same time,we selected 7circ RNAs to verify the data of sequencing by q RT–PCR.Then we detected the bioinformatics and MREs function for studying the role of circ RNAs,on the one hand,bioinformatics analysis was used to analyze GO,KEGG pathway for detecting biological process,cellular component,molecular function and the signal pathway of circ RNAs;on the other hand,we predicting the potential mi RNA binding sites,and drawing the circ RNAs-mi RNA co-expression network maps for detecting the MREs function of the differentially expressed circ RNAs.Results: 1.The bilateral brain tissues of WMD rats were asymmetrical,soft and edematous.2.WMD rats showed obvious cerebral infarction;3.Pathological staining results showed that compared with Sham control group,the lateral ventricle of brain tissue in the WMD experimental group was significantly widened,nerve cells were significantly damaged,and brain tissue structure was disorganized;4.The expression levels of circ RNAs were different between WMD group and Sham control group.Through the analysis of circ RNAs sequencing results,it was found that a total of 107 circ RNAs with significantly differentially expressed circ RNAs were detected with p-value < 0.05 and Fold change ? 2 as the significant difference standard,among which 53 circ RNAs were up-regulated and 54 circ RNAs were down-regulated;5.q PCR was used to verify the significantly differentially expressed circ RNAs in the sequencing results,and the results were consistent with the circ RNAs expression trend in the sequencing results;6.Bioinformatics analysis results showed that GO enrichment analysis showed that 81 biological pathways involved in the parent-gene involvement of differentially expressed circ RNAs in the WMD group were involved in.Molecular functions 96;Biological processes 212.KEGG pathway analysis found that the differentially expressed circ RNAs' parent genes were involved in a total of 23 signaling pathways.Combined with sequencing results,q PCR validation and bioinformatics analysis,circ KCNMA1 was found.circ PLAS2;circ PTK2;circ NRG1 the four circ RNAs may be closely related with WMD,by analyzing the four circ RNAs bioinformatics,found that the genes involved in biological function and signaling pathways: parents c GMP-PKG signaling pathways,mediated the ubiquitin-proteasome proteolytic pathway,PI3K-Akt signaling pathways,Erb B signaling pathways,has been reported literature in WMD plays an important role in the process of development;7.Circ RNA-mi RNA co-expression network analysis results showed that these differentially expressed circrnas had multiple mi RNA binding sites.Among them,there may be interactions between circ KCNMA1 and mi R-211,circ PTK2 and mi R-107,circ NRG1 / circ PLAS2-and mi R-338,which affect the development and outcome of WMD.Conclusions: In this study,we found a large number of differentially expressed circ RNAs between the rats' brain of Sham group and WMD group,the data suggest that the expression profile could be used to research the unknown circ RNA,including their function in the development and progression of WMD.