| Objective Psoriasis is a recurrent polygenic skin disease characterized by the excessive proliferation of keratinocytes,which is clinically manifested as localized or generalized erythema,covered with white scales,accompanied by different degrees of itching.At present,the exact cause of psoriasis is not fully understood,and it is mainly related to genetic factors,endocrine factors,infectious factors and functional disorders.As a common dermatological disease,it is of great significance to find the pathogenesis of psoriasis and related regulatory pathways to control patient condition and improve the prognosis,this topic is based on whole transcriptome sequencing through non-coding RNA comparison and analysis of skin lesion tissue and non-skin lesion tissue in psoriasis patients.Screening of the causative genes and mutation types in patients with psoriasis will lay a theoretical foundation for further explaining the genetic pathogenesis of the disease,gene diagnosis,and gene therapy in the next step.Methods lncRNA,miRNA,circRNA and mRNA in the skin lesion tissue and nonskin lesion tissue of patients with psoriasis were further compared according to the whole transcriptome sequencing results differential expression spectrum.In this study,we will use the method of integrated analysis to further study the expression quantification and differential expression analysis of variousRNAs,and then build a ceRNA regulatory network by targeting the regulatory relationship between each other,identify the signaling pathways and key genes related to psoriasis,and look for the potential pathogenesis of psoriasis.Results The detailed clinical data of psoriasis patients were investigated,and whole transcriptome sequencing was used in the next step to analyze the sequencing results and found that(1)mRNA expression profile analysis found 1183 mRNAs with significant differential expression,including 659 up-regulated mRNAs and 524 downregulated mRNAs.(2)lncRNA expression profile analysis found 1822 lncRNAs with significant differential expression,including 717 up-regulated lncRNAs and 1105down-regulated lncRNAs.(3)circRNA expression profile analysis found 52 circRNAs with significant differential expression,including 30 up-regulated circRNAs and 22 down-regulated circRNAs.(4)miRNA expression profile analysis found 167 miRNAs with significant differential expression,including 91 up-regulated miRNAs and 76 down-regulated miRNAs.(5)Functional enrichment analysis: GO analysis based on differentially expressed mRNA found that there were 1012 genes involved in biological processes,1068 genes involved in cell composition,and 1010 genes involved in molecular functions;and in the KEGG pathway were found The cytokine-cytokine receptor interaction pathway is the most enriched.GO analysis based on differentially expressed lncRNA target genes found that there were 1875 genes involved in biological processes,1995 genes involved in cell composition,and1888 genes involved in molecular functions;it was found that the KEGG pathway plays a role in herpes simplex virus 1 infection Pathways are the most enriched.GO analysis based on differentially expressed circRNA target genes found that there are43 genes involved in biological processes,43 genes involved in cell composition,and42 genes involved in molecular functions;the Alzheimer’s disease pathway in the KEGG pathway was found most enriched.GO analysis based on differentially expressed miRNA target genes found that there were 4208 genes involved in biological processes,4460 genes involved in cell composition,and 4235 genes involved in molecular functions.It was found that the MAPK signaling pathway in the KEGG pathway was the most enriched.(6)Co-expression profiling analysis based on the expression regulation of differential circRNAs and differential miRNAs revealed a total of 772 circRNA-miRNA target pairs,of which 305 were upregulated-up-regulated,244 were up-regulated-down-regulated,and 132 were downregulated and up-regulated,down-regulated-down-regulated expression of 91,and constructed an interaction network map.(7)Co-expression profiling analysis based on the expression regulation of differential lncRNAs and differential miRNAs revealed a total of 52988 lncRNA-miRNA target pairs,of which 10273 were up-regulated-upregulated,8515 were up-regulated and down-regulated,and 18680 were downregulated and up-regulated,down-regulated-down-regulated expression of 15520,and constructed an interaction network map.(8)Co-expression profiling analysis based on the cis expression regulation of differential lncRNAs and differential mRNAs found that there were 165 lncRNA-mRNA cis target pair relationships,including 64 upregulated-up-regulated expression,10 up-regulated-down-regulated expression,and32 down-regulated-up-regulated expression,59 were down-regulated and downregulated,and constructed an interaction network map.(9)Co-expression profiling analysis was performed according to the expression regulation of differential miRNAs and differential mRNAs,and a total of 409 miRNA-mRNA target pairs were found,of which 68 were up-regulated-up-regulated expression,69 were up-regulated and down-regulated,142 were down-regulated and up-regulated,and 130 were downregulated and down-regulated,and constructed an interaction network map.(10)A total of 103 lncRNA-miRNA-mRNA ceRNA networks were screened according to the ceRNA rules,of which 63 were up-regulated-down-regulated-up-regulated and 40 were down-regulated-up-regulated-down-regulated,and constructed an interaction network map.Conclusion(1)This study reveals the new discovery of psoriasis-related non-coding RNAs including mRNA,lncRNA,circRNA and miRNA under the condition of whole transcriptome sequencing,and analyzes the expression profiles of differentRNAs according to the sequencing results,GO enrichment and KEGG pathway analysis found that it is mainly in immunity,metabolism,cytokine pathways,MAPK signaling pathways,suggesting that the above processes and pathways play an important role in the development mechanism of psoriasis.(2)According to the differential expression of mRNA,lncRNA,circRNA and its corresponding miRNA binding site,the corresponding target pair relationship is constructed,the binding site of miRNA is not unique and can bind to multipleRNAs,indicating that the interlinkages between differentRNAs and the change of regulatory expression are related to the incidence of psoriasis.It is further explained that in the occurrence and development of psoriasis,differentially expressed genes may be involved through multiple pathways or different roles.(3)In this study,the ceRNA regulation network of lncRNA-miRNAmRNA differentially expressed in patients with psoriasis was successfully constructed,and the potential mechanism of non-coding RNA in psoriasis was explored.In the constructed psoriasis patient ceRNA network,the four miRNAs common to lncRNA and mRNA are hsa-mi R-449 a,hsa-mi R-3177-3p,hsa-mi R-3940-3p,hsa-mi R-204-3p,the corresponding mRNA is MOV10L1,SPAAR,CYP2A6,RUFY4.(4)There are a total of 103 lncRNAs in the lncRNA-miRNA-mRNA ceRNA regulatory network constructed in this study,and 91 lncRNAs are the first to be reported,LINC01206 and H19 are most likely to be new targets for the treatment of psoriasis in the future.This study provides a new perspective for the study of the pathogenesis of psoriasis,and also provides a reference for the subsequent study of the genetic mechanism of psoriasis. |