Objective:Long non-coding RNAs(lncRNAs)are implicated in multiple pathophysiological processes in placenta-related disorders;however,their expression and function in late-onset pre-eclampsia(LOPE)remain unclear.This s...Objective:Long non-coding RNAs(lncRNAs)are implicated in multiple pathophysiological processes in placenta-related disorders;however,their expression and function in late-onset pre-eclampsia(LOPE)remain unclear.This study aimed to investigate the expression of lncRNAs in LOPE,construct a competing endogenous RNA(ceRNA)network,and identify the pathways associated with LOPE pathogenesis.Methods:We performed lncRNA and mRNAs microarray profiling to identify the differential expression profiles of lncRNAs and mRNAs in LOPE compared to those in normal pregnancy.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was performed to validate differentially expressed genes.Subsequently,we generated an interaction network between lncRNAs,(micro-RNAs)miRNAs,and mRNAs based on the Pearson’s correlation coefficient between lncRNAs and mRNAs.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to understand the functional significance of differentially expressed lncRNAs(DElncRNAs)in LOPE.Results:We identified 29 DElncRNAs(25 upregulated and four downregulated)and 212 differentially expressed mRNAs(DEmRNAs;203 upregulated and nine downregulated)in LOPE placentas.Within them,six lncRNAs and four mRNAs were verified by qRT-PCR.GO and KEGG analyses revealed the potential pathways affected by these mRNAs,such as positive regulation of leukocyte chemotaxis,chemokine signaling pathway,and response to hypoxia.Finally,we constructed a ceRNA network including three DElncRNAs and 124 DEmRNAs,whose competing interactions may be mediated by 17 miRNAs.Two DElncRNAs,ENST00000515376 and ENST00000520544,were found to be hub genes,as they interacted with most miRNAs and mRNAs.ENST00000515376 is most likely related to the metabolic process of arachidonic acid,whereas ENST00000520544 is more likely related to the coagulation system,such as the regulation of blood coagulation and platelet degranulation.Conclusion:Differential expression profile of lncRNAs and the lncRNA-miRNA-mRNA network in LOPE provide potential therapeutic targets for this disease.展开更多
Objective Circular RNAs(circRNAs)have important roles in the development of hepatitis B virus(HBV)-related cirrhosis and hepatocellular carcinoma(HCC);however,they have not been thoroughly researched.Methods In this s...Objective Circular RNAs(circRNAs)have important roles in the development of hepatitis B virus(HBV)-related cirrhosis and hepatocellular carcinoma(HCC);however,they have not been thoroughly researched.Methods In this study,we collected blood samples from patients with HCC and cirrhosis for microarray analysis of serum circRNA expression profiles.The expression levels of four circRNAs were further verified in patients with HBV-related HCC and HBV-related cirrhosis using qRT-PCR.TargetScan,miRanda,and circBank were used to predict the interactions between a selected circRNA,circRNA_00000367,and both miRNAs and mRNAs.An interaction network was generated using Cytoscape to elucidate the correlations among the target microRNAs and mRNAs.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were utilized to interpret the biological functions and signaling pathways of the target genes.Results A cluster analysis revealed 8 up-regulated and 80 down-regulated circRNAs in HCC group compared with the cirrhosis group.Microarray and qRT-PCR analyses showed that circRNA_0000367 expression was significantly lower in patients with HBV-related HCC than in patients with HBV-related cirrhosis.Furthermore,the expression levels of circRNA_0000367 were significantly lower in patients with drug-resistant HBV and HBV-related cirrhosis who progressed to HCC.A circRNA_00000367/miRNA/mRNA network analysis showed that the target genes were involved in various biological processes and signaling pathways.Conclusions CircRNA_0000367 down-regulation in HBV-related cirrhosis may be associated with progression to HCC,providing a potential HBV-related HCC biomarker.展开更多
基金National Natural Sciences Foundation of China(81971408,81801469,81801468,and 81971411)National Key R&D Program of China(2016YFC1000403)2020"Diligence·Excellence"Clinical Innovative Team Project"Study on the comprehensive management of preeclampsia and its pathogenesis"conducted by Obstetrics and Gynecology Hospital of Fudan University(2021fckbc06)
文摘Objective:Long non-coding RNAs(lncRNAs)are implicated in multiple pathophysiological processes in placenta-related disorders;however,their expression and function in late-onset pre-eclampsia(LOPE)remain unclear.This study aimed to investigate the expression of lncRNAs in LOPE,construct a competing endogenous RNA(ceRNA)network,and identify the pathways associated with LOPE pathogenesis.Methods:We performed lncRNA and mRNAs microarray profiling to identify the differential expression profiles of lncRNAs and mRNAs in LOPE compared to those in normal pregnancy.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was performed to validate differentially expressed genes.Subsequently,we generated an interaction network between lncRNAs,(micro-RNAs)miRNAs,and mRNAs based on the Pearson’s correlation coefficient between lncRNAs and mRNAs.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to understand the functional significance of differentially expressed lncRNAs(DElncRNAs)in LOPE.Results:We identified 29 DElncRNAs(25 upregulated and four downregulated)and 212 differentially expressed mRNAs(DEmRNAs;203 upregulated and nine downregulated)in LOPE placentas.Within them,six lncRNAs and four mRNAs were verified by qRT-PCR.GO and KEGG analyses revealed the potential pathways affected by these mRNAs,such as positive regulation of leukocyte chemotaxis,chemokine signaling pathway,and response to hypoxia.Finally,we constructed a ceRNA network including three DElncRNAs and 124 DEmRNAs,whose competing interactions may be mediated by 17 miRNAs.Two DElncRNAs,ENST00000515376 and ENST00000520544,were found to be hub genes,as they interacted with most miRNAs and mRNAs.ENST00000515376 is most likely related to the metabolic process of arachidonic acid,whereas ENST00000520544 is more likely related to the coagulation system,such as the regulation of blood coagulation and platelet degranulation.Conclusion:Differential expression profile of lncRNAs and the lncRNA-miRNA-mRNA network in LOPE provide potential therapeutic targets for this disease.
基金supported financially by the Capital’s Funds for Health Improvement and Research[2022-1-2181]Demonstrating Application and Research of Clinical Diagnosis and Treatment Technology in Beijing[Z221100007422002]+1 种基金Sino-German Mobility Programme[M-0200]Beijing Hospital Authority Youth Programme[QML20211701].
文摘Objective Circular RNAs(circRNAs)have important roles in the development of hepatitis B virus(HBV)-related cirrhosis and hepatocellular carcinoma(HCC);however,they have not been thoroughly researched.Methods In this study,we collected blood samples from patients with HCC and cirrhosis for microarray analysis of serum circRNA expression profiles.The expression levels of four circRNAs were further verified in patients with HBV-related HCC and HBV-related cirrhosis using qRT-PCR.TargetScan,miRanda,and circBank were used to predict the interactions between a selected circRNA,circRNA_00000367,and both miRNAs and mRNAs.An interaction network was generated using Cytoscape to elucidate the correlations among the target microRNAs and mRNAs.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were utilized to interpret the biological functions and signaling pathways of the target genes.Results A cluster analysis revealed 8 up-regulated and 80 down-regulated circRNAs in HCC group compared with the cirrhosis group.Microarray and qRT-PCR analyses showed that circRNA_0000367 expression was significantly lower in patients with HBV-related HCC than in patients with HBV-related cirrhosis.Furthermore,the expression levels of circRNA_0000367 were significantly lower in patients with drug-resistant HBV and HBV-related cirrhosis who progressed to HCC.A circRNA_00000367/miRNA/mRNA network analysis showed that the target genes were involved in various biological processes and signaling pathways.Conclusions CircRNA_0000367 down-regulation in HBV-related cirrhosis may be associated with progression to HCC,providing a potential HBV-related HCC biomarker.
