Analysis Of Maternal Fetal-Derived CeRNA Network Regulation In Trisomy 18 Syndrome

Competing endogenousRNAs（ce RNAs）refer to a group of RNAs that have mi RNA binding sites,are capable of competitively binding mi RNAs,and inhibit mi RNAs from regulating target genes.In fact,ce RNA,not a new RNA molecule,but the latest discovery of a class of RNA with regulatory functions.Which contains m RNA,lnc RNA,pseudogenes,circRNA and sRNA and so on.18-trisomy syndrome is also known as Edwards syndrome.It is a common chromosomal trisomy.It is due to the chromosome aberration caused by the increase of 1 chromosome in human chromosome 18.The clinical manifestations of these children are.The difference is large,ranging from severe congenital malformation to near normal.Severe clinical manifestations are severe disorders of the nervous system development,facial malformations,growth retardation,skeletal abnormalities,heart and kidney malformations.Because of the high spontaneous abortion rate in children with 18-trisomy syndrome during prenatal period,the prevalence of neonatal 18-trisomy syndrome is 1/8 000-1/6 000,second only to Down’s syndrome.The incidence of syndromes（Downsyndrome,DS）has serious mental retardation and multiple defects,life is often unable to take care of themselves,social adaptation and poor labor ability,causing heavy economic burdens on families and society.The creation of a new type of non-invasive prenatal screening is important for finding markers of prenatal diagnosis of trisomy 18 syndrome.This study mainly analyzed the differential expression of circRNA and mi RNA binding sites,the distribution of lnc RNAs in known types of genes,the analysis of lnc RNA differential expression,the analysis of sRNAs and known mi RNAs,and the prediction of novel mi RNAs.Purpose: Differentially expressed lnc RNAs,circRNAs,and mi RNAs in maternal blood（ES-2）and umbilical cord blood（ES-1）were screened by the whole genome sequencing expression profile and differentially expressed circRNAs,lnc RNAs,sRNAs,and m RNAs,miRNAs Correlative analysis was performed to investigate the network regulation and action mechanism of ce RNA in 18-trisomy syndrome.Method: The peripheral blood and umbilical cord blood of 2 pregnant women with prenatal diagnosis of trisomy 18 syndrome were selected.The control group was normal pregnant women with peripheral blood and umbilical cord blood during the same pregnancy cycle.Total RNA was extracted using the Trizol method using Nano Drop ND.The-1000 was tested for RNA degradation and RNA concentration was determined;DEGseq was used to analyze the differential expression profiles of circRNA,Lnc RNA,and sRNA in peripheral blood and cord blood of pregnant women with trisomy 18 syndrome.Based on the possible interaction between circRNA,Lnc RNA and sRNA and mi RNA and m RNA,the possible association between circRNA,Lnc RNA and sRNA and m RNA in the peripheral blood and cord blood of pregnant women with trisomy 18 syndrome was analyzed.Results:（1）Analysis of circulatory expression profiles of umbilical cord blood in pregnant women with trisomy 18 syndrome revealed 10050 circRNAs with significant differences,of which 5164 were circRNAs and 4886 were transcripts.（2）The circRNA expression profiles of pregnant women with trisomy 18 syndrome revealed 13278 circRNAs with significant difference in expression.Among them,5007 circRNAs were down-regulated and 8271 circRNAs were up-regulated.（3）Analysis of umbilical cord blood and peripheral blood circRNA expression profiles in pregnant women with trisomy 18 syndrome revealed a common difference of 2876,but only 1510 were up-regulated in the same direction,which together down-regulated the expression of circRNA by 1064 and collectively up-regulated circRNA expression.466,of which hg38_circ₀012295 has the largest difference of multiples.（4）Analysis of cord blood lnc RNA expression profiles in pregnant women with trisomy 18 syndrome revealed a significant 1824 differentially expressed lnc RNAs,of which 858 were lnc RNAs downregulated and 966 were upregulated.Analysis of peripheral blood lnc RNA expression profiles of pregnant women with trisomy 18 syndrome revealed that 1063 lnc RNAs were significantly differently expressed,of which 628 were lnc RNAs down-regulated and 135 lnc RNAs were up-regulated.There were 586 lnc RNAs with different expressions in peripheral blood and cord blood.Lnc RNA-m RNA analysis associated with chromosome 18 in cord blood showed that there were 114 genes associated with 65 lnc RNAs,of which RP11-231E4.5 had the most association with lnc RNA-m RNA of CNDP2 gene.Five key genes were selected: CTD-2561J22.5 、RP11-203J24.8、JPX、LINC00998 、RP11-231E4.5.These five key genes were not only significantly different in umbilical cord blood.And in the pregnant woman’s peripheral blood also have the same performance.（5）Analysis of the relationship between sRNA and mi RNA expression profiles revealed hsa-mi R-148b-3p,hsa-mi R-15a-5p,hsa-mi R-15b-3p,hsa-mi R-182-5p,hsa-There were 10 differentially expressed mi RNAs in mi R-199a-3p,hsa-mi R-20a-5p,hsa-mi R-4433a-3p,hsa-mi R-4433b-5p,hsa-mi R-7706 and hsa-mi R-941,especially The hsa-mi R-20a-5p regulates the expression of the corresponding target gene m RNA with the greatest multiple of difference.（6）Selection of trisomy 18 syndrome umbilical cord blood and maternal peripheral blood ce RNA differentially expressed together with m RNA common key node 23 mi RNAs（hsa-mi R-148a-3p,hsa-mi R-148b-3p,hsa-mi R-3184-3p,hsa-mi R-423-5p,hsa-mi R-500a-3p,hsa-mi R-7706,hsa-mi R-941,hsa-mi R-125b-5p,hsa-mi R-1306-5p,hsa-mi R-136-3p,hsa-mi R-148b-3p,hsa-mi R-15a-5p,hsa-mi R-15b-5p,hsa-mi R-199a-5p,hsa-mi R-199b-5p,hsa-mi R-21-3p,hsa-mi R-23a-3p,hsa-mi R-361-3p,hsa-mi R-382-3p,hsa-mi R-424-5p,hsa-mi R-483-3p,hsa-mi R-624-5p,hsa-mi R-941,hsa-mi R-96-5p,hsa-mi R-27a-3p）These key nodes are the central hubs for the interaction of ce RNAs with mi RNAs,mi RNAs,and m RNAs.The ways regulate,interact,and interact.（7）GO analysis of differentially expressed genes revealed 9131 genes involved in biological processes,1201 genes involved in cell composition,and 2321 genes involved in molecular function;Pathway pathway analysis of differential genes and selection of enriched genes Analysis of the top 20 pathways revealed that the phagocytosis pathway in umbilical cord blood and peripheral blood was most enriched.Conclusion:（1）Differentially expressed circRNA,lncRNA and sRNA have their corresponding mi RNA binding sites,and there may be more than one,and the binding site may also be a common site of other ce RNAs.Through the interaction with mi RNAs,they can jointly control the target.Gene expression.These ce RNAs may become new molecular biological markers for trisomy 18 syndrome in the future.（2）Differentially expressed genes may participate in the occurrence of 18-trisomy syndrome through multiple pathways and roles.（3）CTD-2561J22.5、RP11-203J24.8、JPX、LINC00998 、RP11-231E4.5,5 dysregulated lnc RNAs may have important effects on the occurrence and development of 18-trisomy syndrome.（4）The 23 mi RNAs at key nodes were selected to regulate,interact,and interact with each other in different ways through the interaction of ce RNAs with mi RNAs,mi RNAs,and m RNAs,among which hsa-mi R-148b-3p and hsa-mi R-941 It is most likely to be a biomarker for the diagnosis of 18-trisomy syndrome.