目的通过生物信息学方法分析参与高脂饮食损伤甲状腺功能的miRNA-mRNA调控网络,为早期干预脂毒性损伤甲状腺功能提供新的靶点。方法给予大鼠高脂饮食8周,建立甲状腺功能损伤大鼠模型,以正常饮食组为对照,Agilent芯片检测甲状腺miRNA和m...目的通过生物信息学方法分析参与高脂饮食损伤甲状腺功能的miRNA-mRNA调控网络,为早期干预脂毒性损伤甲状腺功能提供新的靶点。方法给予大鼠高脂饮食8周,建立甲状腺功能损伤大鼠模型,以正常饮食组为对照,Agilent芯片检测甲状腺miRNA和mRNA表达,RStudio的limma包筛选差异miRNA和mRNA。miRwalk预测差异miRNA调控的潜在下游靶基因,利用微生信网站将预测的靶基因和差异mRNA取交集,建立差异miRNA-差异mRNA网络。通过在线网站Metascape对交集mRNA进行基因本体论(gene ontology,GO)注释和京都基因和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路分析。利用String在线网站进行蛋白质-蛋白质相互作用(protein-protein interaction,PPI)分析,使用Cytoscape可视化PPI网络,CytoNCA插件筛选枢纽基因。基于关键基因建立高脂饮食损伤甲状腺功能的潜在miRNA-mRNA网络。结果筛选出27个上调和6个下调miRNA,775个上调和543个下调mRNA,下调miRNA的靶点mRNA与芯片筛选的上调mRNA有301个重叠,上调miRNA的靶点mRNA与芯片筛选的下调mRNA有278个重叠,分别获得491和777个miRNA-mRNA对。GO和KEGG分析发现差异mRNA富集到与甲状腺激素合成和细胞增殖等相关通路。进一步筛选出Src、Pebp1、Il1b、Plcg1、Igf1、Ntrk2等10个枢纽基因,建立了包括miR-3473/Src、miR-339-3p/Igf1、miR-674-5p/Igf1、miR-339-3p/Ntrk2、miR-99b-3p/Ntrk2等的关键miRNA-mRNA调控对。结论miR-3473、Igf1和Ntrk2等可能作为核心miRNA和mRNA,参与调控高脂饮食损伤甲状腺功能。展开更多
Acute myocardial infarction(AMI)is a severe cardiovascular disease.This study aimed to identify crucial microRNAs(miRNAs)and mRNAs in AMI by establishing a miRNA-mRNA network.The microarray datasets GSE31568,GSE148153...Acute myocardial infarction(AMI)is a severe cardiovascular disease.This study aimed to identify crucial microRNAs(miRNAs)and mRNAs in AMI by establishing a miRNA-mRNA network.The microarray datasets GSE31568,GSE148153,and GSE66360 were downloaded from the Gene Expression Omnibus(GEO)database.We identified differentially expressed miRNAs(DE-miRNAs)and mRNAs(DE-mRNAs)in AMI samples compared with normal control samples.The consistently changing miRNAs in both GSE31568 and GSE148153 datasets were selected as candidate DE-miRNAs.The interactions between the candidate DE-miRNAs and DE-mRNAs were analyzed,and a miRNA-mRNA network and a protein-protein interaction network were constructed,along with functional enrichment and pathway analyses.A total of 209 DE-miRNAs in the GSE31568 dataset,857 DE-miRNAs in the GSE148153 dataset,and 351 DE-mRNAs in the GSE66360 dataset were identified.Eighteen candidate DE-miRNAs were selected from both the GSE31568 and GSE148153 datasets.Furthermore,miR-646,miR-127-5p,miR-509-5p,miR-509-3-5p,and miR-767-5p were shown to have a higher degree in the miRNA-mRNA network.THBS-1 as well as FOS was a hub gene in the miRNA-mRNA network and the protein-protein interaction(PPI)network,respectively.CDKN1A was important in both miRNA-mRNA network and PPI network.We established a miRNA-mRNA network in AMI and identified five miRNAs and three genes,which might be used as biomarkers and potential therapeutic targets for patients with AMI.展开更多
BACKGROUND The high morbidity and mortality of colorectal cancer(CRC)have posed great threats to human health.Circular RNA(CircRNA)and microRNA(miRNA),acting as competing endogenous RNAs(ceRNAs),have been found to pla...BACKGROUND The high morbidity and mortality of colorectal cancer(CRC)have posed great threats to human health.Circular RNA(CircRNA)and microRNA(miRNA),acting as competing endogenous RNAs(ceRNAs),have been found to play vital roles in carcinogenesis.However,the biological function of ceRNAs in CRC pathogenesis and prognosis remains largely unexplored.AIM To identify the CRC-specific circRNA-miRNA-mRNA regulatory network and uncover the subnetwork associated with its prognosis.METHODS CircRNAs,miRNAs and mRNAs differentially expressed(DE)in CRC tissues were selected by expression file analysis in the Gene Expression Omnibus(GEO)database,and the downstream target molecules of circRNAs and miRNAs were predicted.Then,the intersection of differentially expressed RNA molecules with the predicted targets was determined to obtain a ceRNA network.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to elucidate the possible mechanism of pathogenesis.A survival analysis using the gene profiles and clinical information in The Cancer Genome Atlas(TCGA)database was performed to identify the mRNAs associated with the clinical outcome of CRC patients and construct a prognostic subnetwork.RESULTS We downloaded three datasets(GSE126095,GSE41655 and GSE41657)of largescale CRC samples from the GEO database.There were 55 DEcircRNAs,114 DEmiRNAs and 267 DEmRNAs in CRC tissues compared with normal tissues.After intersecting these molecules with predicted targets,19 circRNAs,13 miRNAs and 28 mRNAs were chosen to develop a circRNA-miRNA-mRNA network.GO and KEGG functional enrichment analyses indicated that the retinol metabolic process,leukocyte chemotaxis,extracellular matrix remodeling,endoplasmic reticulum stress,alcohol dehydrogenase activity,gastric acid secretion,nitrogen metabolism and NOD-like receptor signaling pathway might participate in the tumorigenesis of CRC.After verifying the identified mRNA effect in the TCGA database,we finally recognized 3 mRNAs(CA2,ITLN1 and LRRC19)that were significantly associated with the overall survival of CRC patients and constructed a ceRNA subnetwork including 5 circRNAs(hsa_circ_0080210,hsa_circ_0007158,hsa_circ_0000375,hsa_circ_0018909 and hsa_circ_0011536)and 3 miRNAs(hsa-miR-601,hsa-miR-671-5p and hsa-miR-765),which could contain innovative and noninvasive indicators for the early screening and prognostic prediction of CRC.CONCLUSION We proposed a circRNA-miRNA-mRNA regulatory network closely associated with the progression and clinical outcome of CRC that might include promising biomarkers for carcinogenesis and therapeutic targets.展开更多
[Objectives]To further explore the mechanism of quercetin regulating the activity of Sune-1 cells.[Methods]High-throughput mRNA-miRNA transcriptome sequencing technology was used to screen miRNA in Sune-1 cells treate...[Objectives]To further explore the mechanism of quercetin regulating the activity of Sune-1 cells.[Methods]High-throughput mRNA-miRNA transcriptome sequencing technology was used to screen miRNA in Sune-1 cells treated with quercetin.[Results]Statistical analysis showed that 1264 miRNAs were differentially expressed in Sune-1 cells treated with quercetin,of which 716 were significantly up-regulated and 548 were significantly down-regulated;191 miRNAs were differentially expressed in Sune-1 cells treated with quercetin,of which 129 were significantly up-regulated and 62 were significantly down-regulated.By comparing the expression differences of these mRNAs and miRNAs in different samples,six different expression patterns were clustered.The expression of the above miRNAs was verified by real-time quantitative PCR(qPCR),and the results were highly consistent with the transcriptome sequencing data.In addition,Gene Ontology annotation and functional enrichment analysis of miRNA target genes showed that CTGF,VHL and H19,which are related to the regulation of cell proliferation signal transduction,were predicted to be new targets of differential miRNAs such as miR494-3p and miR675-3p and may play an important regulatory role in the process of Quercetin inhibiting the proliferation of Sune-1 cells.[Conclusions]This study provides a basis for the rational use of anti-tumor functional components of traditional Chinese medicine,and also provides a theoretical basis for the targeted therapy of nasopharyngeal carcinoma.展开更多
Objectives:Recently,we and others have demonstrated the involvement of Zinc Finger Antisense 1(ZFAS1)in cancer development.However,the intricate interplay of ZFAS1 with miRNAs and mRNAs remains to be fully understood....Objectives:Recently,we and others have demonstrated the involvement of Zinc Finger Antisense 1(ZFAS1)in cancer development.However,the intricate interplay of ZFAS1 with miRNAs and mRNAs remains to be fully understood.Materials and methods:We followed PRISMA guidelines to retrieve and assess the available literature on the topic“ZFAS1/miRNA/mRNA axis”and“Cancer”from databases such as PubMed,Google Scholar,and ScienceDirect.We also used bioinformatic webtools for analyzing the potential miRNA targets of ZFAS1 and its role in survival of cancer patients along with their role in various biological functions and pathways.Results:Our literature search and bioinformatic analysis reveals that ZFAS1 serves as a sponge for numerous miRNAs.Among the various targeted miRNAs,miR-150-5p stands out as significantly correlated with ZFAS1 across multiple databases(p-value=3.27e-16,R-value=-0.346).Additionally,our Kaplan-Meier survival analysis indicates a noteworthy association between ZFAS1 expression levels and overall poor prognosis and survival rates in ovarian,sarcoma,and pancreatic cancers.We also underscore the involvement of various signaling pathways,including Signal Transducer and Activator of Transcription 3(STAT3),Spindle and Kinetochore-associated Protein 1(SKA1),Lysophosphatidic acid receptor 1(LPAR1),and Wntβ-catenin,in cancer development through the ZFAS1/miRNAs/mRNAs axis.Furthermore,we identify ZFAS1’s pivotal roles in diverse molecular processes,such as RNA binding and ribonucleoprotein formation.Conclusion:In conclusion,this review comprehensively summarizes the latest advancements in understanding the regulatory relationships among ZFAS1,miRNAs,and mRNAs,emphasizing their collective role in cancer development to propose innovative avenues for cancer treatment.We believe that the intricate relationship among the ZFAS1-miRNA-mRNA axis may yield potential therapeutic targets for effective cancer management.展开更多
As crucial negative regulatory small non-coding molecules, microRNAs (miRNAs), have multiple biological roles. The abnormal expression of specific miRNAs may contribute to the occurrence and development of tumor. Here...As crucial negative regulatory small non-coding molecules, microRNAs (miRNAs), have multiple biological roles. The abnormal expression of specific miRNAs may contribute to the occurrence and development of tumor. Here, based on HepG2 and L02 cells, we attempted to demonstrate the potential regulatory network of aberrantly expressed miRNA profiles, interaction between miRNA and mRNA, and potential functional correlation between different miRNAs. De-regulated miRNA and mRNA expression profiles were completely surveyed and identified by applying deep sequenc-ing and microarray techniques, respectively. The genome-wide and integrative analysis of miRNA-mRNA was performed based on their functional relationship according to experimentally validated and predicted targets. Nearly 50% targets were negatively regulated by at least 2 aberrantly expressed miRNAs. Similar results were obtained based on experimentally validated and predicted targets. Compared with abnormal miRNAs, their targets showed various expression patterns: stably expressed, down-regulated or up-regulated. Although the theoretical potential miRNA-mRNA interaction could be predicted, they showed consistent or inconsistent expression patterns. Both functional enrichment analysis of target mRNAs of dysregulated miRNAs and abnormal mRNA profiles suggested that corresponding pathways were involved in tumorigenesis. Moreover, to obtain potential functional relationships between different miRNAs, we also performed expression analysis of homologous miRNAs in gene families. Generally, they could co-regulate biological processes with similar roles. The integrative analysis of miRNA-mRNA indicated a complex and flexible regulatory network. The robust network mainly derived from multiple targets for a specific miRNA (and vice versa), each mRNA and co-regulation roles of different miRNAs.展开更多
文摘目的通过生物信息学方法分析参与高脂饮食损伤甲状腺功能的miRNA-mRNA调控网络,为早期干预脂毒性损伤甲状腺功能提供新的靶点。方法给予大鼠高脂饮食8周,建立甲状腺功能损伤大鼠模型,以正常饮食组为对照,Agilent芯片检测甲状腺miRNA和mRNA表达,RStudio的limma包筛选差异miRNA和mRNA。miRwalk预测差异miRNA调控的潜在下游靶基因,利用微生信网站将预测的靶基因和差异mRNA取交集,建立差异miRNA-差异mRNA网络。通过在线网站Metascape对交集mRNA进行基因本体论(gene ontology,GO)注释和京都基因和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路分析。利用String在线网站进行蛋白质-蛋白质相互作用(protein-protein interaction,PPI)分析,使用Cytoscape可视化PPI网络,CytoNCA插件筛选枢纽基因。基于关键基因建立高脂饮食损伤甲状腺功能的潜在miRNA-mRNA网络。结果筛选出27个上调和6个下调miRNA,775个上调和543个下调mRNA,下调miRNA的靶点mRNA与芯片筛选的上调mRNA有301个重叠,上调miRNA的靶点mRNA与芯片筛选的下调mRNA有278个重叠,分别获得491和777个miRNA-mRNA对。GO和KEGG分析发现差异mRNA富集到与甲状腺激素合成和细胞增殖等相关通路。进一步筛选出Src、Pebp1、Il1b、Plcg1、Igf1、Ntrk2等10个枢纽基因,建立了包括miR-3473/Src、miR-339-3p/Igf1、miR-674-5p/Igf1、miR-339-3p/Ntrk2、miR-99b-3p/Ntrk2等的关键miRNA-mRNA调控对。结论miR-3473、Igf1和Ntrk2等可能作为核心miRNA和mRNA,参与调控高脂饮食损伤甲状腺功能。
基金supported by the funds from the National Natural Science Foundation of China(Grant No.81871359 and No.81800445).
文摘Acute myocardial infarction(AMI)is a severe cardiovascular disease.This study aimed to identify crucial microRNAs(miRNAs)and mRNAs in AMI by establishing a miRNA-mRNA network.The microarray datasets GSE31568,GSE148153,and GSE66360 were downloaded from the Gene Expression Omnibus(GEO)database.We identified differentially expressed miRNAs(DE-miRNAs)and mRNAs(DE-mRNAs)in AMI samples compared with normal control samples.The consistently changing miRNAs in both GSE31568 and GSE148153 datasets were selected as candidate DE-miRNAs.The interactions between the candidate DE-miRNAs and DE-mRNAs were analyzed,and a miRNA-mRNA network and a protein-protein interaction network were constructed,along with functional enrichment and pathway analyses.A total of 209 DE-miRNAs in the GSE31568 dataset,857 DE-miRNAs in the GSE148153 dataset,and 351 DE-mRNAs in the GSE66360 dataset were identified.Eighteen candidate DE-miRNAs were selected from both the GSE31568 and GSE148153 datasets.Furthermore,miR-646,miR-127-5p,miR-509-5p,miR-509-3-5p,and miR-767-5p were shown to have a higher degree in the miRNA-mRNA network.THBS-1 as well as FOS was a hub gene in the miRNA-mRNA network and the protein-protein interaction(PPI)network,respectively.CDKN1A was important in both miRNA-mRNA network and PPI network.We established a miRNA-mRNA network in AMI and identified five miRNAs and three genes,which might be used as biomarkers and potential therapeutic targets for patients with AMI.
基金Supported by National Key Development Plan for Precision Medicine Research,No.2017YFC0910002.
文摘BACKGROUND The high morbidity and mortality of colorectal cancer(CRC)have posed great threats to human health.Circular RNA(CircRNA)and microRNA(miRNA),acting as competing endogenous RNAs(ceRNAs),have been found to play vital roles in carcinogenesis.However,the biological function of ceRNAs in CRC pathogenesis and prognosis remains largely unexplored.AIM To identify the CRC-specific circRNA-miRNA-mRNA regulatory network and uncover the subnetwork associated with its prognosis.METHODS CircRNAs,miRNAs and mRNAs differentially expressed(DE)in CRC tissues were selected by expression file analysis in the Gene Expression Omnibus(GEO)database,and the downstream target molecules of circRNAs and miRNAs were predicted.Then,the intersection of differentially expressed RNA molecules with the predicted targets was determined to obtain a ceRNA network.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to elucidate the possible mechanism of pathogenesis.A survival analysis using the gene profiles and clinical information in The Cancer Genome Atlas(TCGA)database was performed to identify the mRNAs associated with the clinical outcome of CRC patients and construct a prognostic subnetwork.RESULTS We downloaded three datasets(GSE126095,GSE41655 and GSE41657)of largescale CRC samples from the GEO database.There were 55 DEcircRNAs,114 DEmiRNAs and 267 DEmRNAs in CRC tissues compared with normal tissues.After intersecting these molecules with predicted targets,19 circRNAs,13 miRNAs and 28 mRNAs were chosen to develop a circRNA-miRNA-mRNA network.GO and KEGG functional enrichment analyses indicated that the retinol metabolic process,leukocyte chemotaxis,extracellular matrix remodeling,endoplasmic reticulum stress,alcohol dehydrogenase activity,gastric acid secretion,nitrogen metabolism and NOD-like receptor signaling pathway might participate in the tumorigenesis of CRC.After verifying the identified mRNA effect in the TCGA database,we finally recognized 3 mRNAs(CA2,ITLN1 and LRRC19)that were significantly associated with the overall survival of CRC patients and constructed a ceRNA subnetwork including 5 circRNAs(hsa_circ_0080210,hsa_circ_0007158,hsa_circ_0000375,hsa_circ_0018909 and hsa_circ_0011536)and 3 miRNAs(hsa-miR-601,hsa-miR-671-5p and hsa-miR-765),which could contain innovative and noninvasive indicators for the early screening and prognostic prediction of CRC.CONCLUSION We proposed a circRNA-miRNA-mRNA regulatory network closely associated with the progression and clinical outcome of CRC that might include promising biomarkers for carcinogenesis and therapeutic targets.
基金Supported by Educational Research Project for Young and Middle-aged Teachers in Fujian Province(Science and Technology Category,JAT210477)。
文摘[Objectives]To further explore the mechanism of quercetin regulating the activity of Sune-1 cells.[Methods]High-throughput mRNA-miRNA transcriptome sequencing technology was used to screen miRNA in Sune-1 cells treated with quercetin.[Results]Statistical analysis showed that 1264 miRNAs were differentially expressed in Sune-1 cells treated with quercetin,of which 716 were significantly up-regulated and 548 were significantly down-regulated;191 miRNAs were differentially expressed in Sune-1 cells treated with quercetin,of which 129 were significantly up-regulated and 62 were significantly down-regulated.By comparing the expression differences of these mRNAs and miRNAs in different samples,six different expression patterns were clustered.The expression of the above miRNAs was verified by real-time quantitative PCR(qPCR),and the results were highly consistent with the transcriptome sequencing data.In addition,Gene Ontology annotation and functional enrichment analysis of miRNA target genes showed that CTGF,VHL and H19,which are related to the regulation of cell proliferation signal transduction,were predicted to be new targets of differential miRNAs such as miR494-3p and miR675-3p and may play an important regulatory role in the process of Quercetin inhibiting the proliferation of Sune-1 cells.[Conclusions]This study provides a basis for the rational use of anti-tumor functional components of traditional Chinese medicine,and also provides a theoretical basis for the targeted therapy of nasopharyngeal carcinoma.
文摘Objectives:Recently,we and others have demonstrated the involvement of Zinc Finger Antisense 1(ZFAS1)in cancer development.However,the intricate interplay of ZFAS1 with miRNAs and mRNAs remains to be fully understood.Materials and methods:We followed PRISMA guidelines to retrieve and assess the available literature on the topic“ZFAS1/miRNA/mRNA axis”and“Cancer”from databases such as PubMed,Google Scholar,and ScienceDirect.We also used bioinformatic webtools for analyzing the potential miRNA targets of ZFAS1 and its role in survival of cancer patients along with their role in various biological functions and pathways.Results:Our literature search and bioinformatic analysis reveals that ZFAS1 serves as a sponge for numerous miRNAs.Among the various targeted miRNAs,miR-150-5p stands out as significantly correlated with ZFAS1 across multiple databases(p-value=3.27e-16,R-value=-0.346).Additionally,our Kaplan-Meier survival analysis indicates a noteworthy association between ZFAS1 expression levels and overall poor prognosis and survival rates in ovarian,sarcoma,and pancreatic cancers.We also underscore the involvement of various signaling pathways,including Signal Transducer and Activator of Transcription 3(STAT3),Spindle and Kinetochore-associated Protein 1(SKA1),Lysophosphatidic acid receptor 1(LPAR1),and Wntβ-catenin,in cancer development through the ZFAS1/miRNAs/mRNAs axis.Furthermore,we identify ZFAS1’s pivotal roles in diverse molecular processes,such as RNA binding and ribonucleoprotein formation.Conclusion:In conclusion,this review comprehensively summarizes the latest advancements in understanding the regulatory relationships among ZFAS1,miRNAs,and mRNAs,emphasizing their collective role in cancer development to propose innovative avenues for cancer treatment.We believe that the intricate relationship among the ZFAS1-miRNA-mRNA axis may yield potential therapeutic targets for effective cancer management.
文摘As crucial negative regulatory small non-coding molecules, microRNAs (miRNAs), have multiple biological roles. The abnormal expression of specific miRNAs may contribute to the occurrence and development of tumor. Here, based on HepG2 and L02 cells, we attempted to demonstrate the potential regulatory network of aberrantly expressed miRNA profiles, interaction between miRNA and mRNA, and potential functional correlation between different miRNAs. De-regulated miRNA and mRNA expression profiles were completely surveyed and identified by applying deep sequenc-ing and microarray techniques, respectively. The genome-wide and integrative analysis of miRNA-mRNA was performed based on their functional relationship according to experimentally validated and predicted targets. Nearly 50% targets were negatively regulated by at least 2 aberrantly expressed miRNAs. Similar results were obtained based on experimentally validated and predicted targets. Compared with abnormal miRNAs, their targets showed various expression patterns: stably expressed, down-regulated or up-regulated. Although the theoretical potential miRNA-mRNA interaction could be predicted, they showed consistent or inconsistent expression patterns. Both functional enrichment analysis of target mRNAs of dysregulated miRNAs and abnormal mRNA profiles suggested that corresponding pathways were involved in tumorigenesis. Moreover, to obtain potential functional relationships between different miRNAs, we also performed expression analysis of homologous miRNAs in gene families. Generally, they could co-regulate biological processes with similar roles. The integrative analysis of miRNA-mRNA indicated a complex and flexible regulatory network. The robust network mainly derived from multiple targets for a specific miRNA (and vice versa), each mRNA and co-regulation roles of different miRNAs.
