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
Dysregulation of post-transcriptional regulation of gene expression has been found to influence various human disorders. Aberrant miRNA-based regulation of gene expression has been found to be associated with differen...Dysregulation of post-transcriptional regulation of gene expression has been found to influence various human disorders. Aberrant miRNA-based regulation of gene expression has been found to be associated with different cancers, including breast cancers. Very little information is available on the effect of dysregulation of miRNA-mediated regulation on luminal B breast cancer. This study was aimed at comprehending the regulation of gene expression through miRNA in luminal B breast cancers by comprehensive analysis of miRNA and mRNA expression data together. Negatively regulated miRNA-target gene pairs were identified, and the target genes were functionally enriched to identify critical pathways associated with luminal B breast cancer. Further, the prognostic significance of these miRNAs and target gene pairs was assessed to identify genes with prognostic value in luminal B breast cancer. A total of 266 differentially expressed miRNAs and 164 dysregulated miRNA-target gene pairs were identified. Four genes, including SRP9, DSN1, RACGAP1, and SLC10A6, and one miRNA, hsa-mir-421, showed significant influence on the prognosis of patients with luminal B breast cancer. Through additional experimental examination of these findings, a deeper comprehension of miRNA-based post-transcriptional regulation in luminal B breast tumors will be possible.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
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.
文摘Dysregulation of post-transcriptional regulation of gene expression has been found to influence various human disorders. Aberrant miRNA-based regulation of gene expression has been found to be associated with different cancers, including breast cancers. Very little information is available on the effect of dysregulation of miRNA-mediated regulation on luminal B breast cancer. This study was aimed at comprehending the regulation of gene expression through miRNA in luminal B breast cancers by comprehensive analysis of miRNA and mRNA expression data together. Negatively regulated miRNA-target gene pairs were identified, and the target genes were functionally enriched to identify critical pathways associated with luminal B breast cancer. Further, the prognostic significance of these miRNAs and target gene pairs was assessed to identify genes with prognostic value in luminal B breast cancer. A total of 266 differentially expressed miRNAs and 164 dysregulated miRNA-target gene pairs were identified. Four genes, including SRP9, DSN1, RACGAP1, and SLC10A6, and one miRNA, hsa-mir-421, showed significant influence on the prognosis of patients with luminal B breast cancer. Through additional experimental examination of these findings, a deeper comprehension of miRNA-based post-transcriptional regulation in luminal B breast tumors will be possible.
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.
