A Novel circRNA-miRNA-mRNA Hub Regulatory Network in Lung Adenocarcinoma.
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ABSTRACT:
SUBMITTER: Zuo H
PROVIDER: S-EPMC8292838 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNumerous studies have identified that circular RNAs (circRNAs) can serve as competing endogenous RNAs (ceRNAs) to regulate tumor progression. However, there are still a large number of circRNAs to be deciphered.ObjectiveThe purpose of this study was to reveal novel circRNAs and their potential role in lung adenocarcinoma (LUAD).MethodsTo unveil LUAD-related circRNAs, microRNA (miRNAs), and messenger RNA (mRNA) and elucidate their possible molecular mechanisms, we employed a strategy combining extensive data mining and bioinformatics methods. According to the results of bioinformatics workflow analysis, a novel circRNA-miRNA-mRNA network was constructed.ResultsTen circRNAs with different expressions were acquired from four Gene Expression Omnibus (GEO) microarray datasets. Seven Prognostic-related differential miRNAs of LUAD were gained from The Cancer Genome Atlas (TCGA). Simultaneously, the miRNA reaction components corresponding to the ten circRNAs were predicted. Two circRNA-miRNA interactions including two circRNAs (hsa_circ_0008234 and hsa_circ_0002360) and two miRNAs (hsa-miR-490-3p and hsa-miR-1293) were identified above. Then, target genes of the two miRNAs and differently expressed genes (DEGs) from TCGA on LUAD were collected. Three hub-genes (ADCY9, NMUR1, SYT1) were determined according to prognosis in patients with LUAD ulteriorly.Conclusionshsa_circ_0008234/hsa-miR-490-3p/SYT1 and hsa_circ_0002360/hsa-miR-1293/ (ADCY9, NMUR1) networks were established, and identified molecules may be involved in pathogenesis and prognosis in patients with LUAD.
| S-EPMC9141977 | biostudies-literature
Project description:AimThis study aimed to investigate the expression profiles of circRNAs and candidate circRNA-miRNA-mRNA network in BC.MethodsDifferentially expressed circRNAs, miRNAs, and mRNAs (DEcircRNAs, DEmiRNAs, and DEmRNAs) between BC and normal breast tissue samples were screened by analyzing raw data of the RNA sequencing profile. The expression levels of hub genes in 48 pairs of cancerous and tumor-free breast tissues surgically resected from BC patients were determined by RT-qPCR analysis.ResultsA total of 145 DEcircRNAs, 140 DEmiRNAs, and 2451 DEmRNAs between BC and normal breast tissue samples were screened out. There were 5 pairs of upcircRNA-downmiRNA-upmRNA network and 20 pairs of downcircRNA-upmiRNA-downmRNA network. EIF4EBP1, DUSP1, EGR2, EZH1, and CBX7 were found to be correlated with overall survival of the patients with BC. The expression level of EIF4EBP1 was increased and the expression levels of DUSP1, EGR2, EZH1, and CBX7 were decreased in cancerous breast tissues compared to tumor-free breast tissues (p < 0.0001). The RT-qPCR results from 48 BC patients were consistent with the bioinformatics results.ConclusionThis study provides a novel perspective to study circRNA-miRNA-mRNA network in BC and assists in the identification of new potential biomarkers to be used for diagnostic and prognostic purposes.
| S-EPMC8570857 | biostudies-literature
Project description:BackgroundGlioma is the most common brain neoplasm with a poor prognosis. Circular RNA (circRNA) and their associated competing endogenous RNA (ceRNA) network play critical roles in the pathogenesis of glioma. However, the alteration of the circRNA-miRNA-mRNA regulatory network and its correlation with glioma therapy haven't been systematically analyzed.MethodsWith GEO, GEPIA2, circBank, CSCD, CircInteractome, mirWalk 2.0, and mirDIP 4.1, we constructed a circRNA-miRNA-mRNA network in glioma. LASSO regression and multivariate Cox regression analysis established a hub mRNA signature to assess the prognosis. GSVA was used to estimate the immune infiltration level. Potential anti-glioma drugs were forecasted using the cMap database and evaluated with GSEA using GEO data.ResultsA ceRNA network of seven circRNAs (hsa_circ_0030788/0034182/0000227/ 0018086/0000229/0036592/0002765), 15 miRNAs(hsa-miR-1200/1205/1248/ 1303/3925-5p/5693/581/586/599/607/640/647/6867-5p/767-3p/935), and 46 mRNAs (including 11 hub genes of ARHGAP11A, DRP2, HNRNPA3, IGFBP5, IP6K2, KLF10, KPNA4, NRP2, PAIP1, RCN1, and SEMA5A) was constructed. Functional enrichment showed they influenced majority of the hallmarks of tumors. Eleven hub genes were proven to be decent prognostic signatures for glioma in both TCGA and CGGA datasets. Forty-six LASSO regression significant genes were closely related to immune infiltration. Finally, five compounds (fulvestrant, tanespimycin, mifepristone, tretinoin, and harman) were predicted as potential treatments for glioma. Among them, mifepristone and tretinoin were proven to inhibit the cell cycle and DNA repair in glioma.ConclusionThis study highlights the potential pathogenesis of the circRNA-miRNA-mRNA regulatory network and identifies novel therapeutic options for glioma.
| S-EPMC8351580 | biostudies-literature
Project description:Circular RNA (circRNA) abnormal expression and regulation are involved in the occurrence and development of a variety of tumors. However, the role of circRNAs still remains unknown in gastrointestinal stromal tumors (GISTs). In the present study, the differential circRNA expression profile of GISTs was screened by human circRNAs chip and verified by qRT-PCR. The circRNA-miRNA-mRNA regulatory network was constructed using the cytoHubba plugin based on the Cytoscape software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore circRNA functions. Six significantly differential circRNAs were also verified in 20 pairs of GISTs and adjacent tissues by qRT-PCR. The result showed that a total of 543 differentially expressed circRNAs were identified in GISTs, of which 242 were up-regulated and 301 were down-regulated. Additionally, the circRNA-miRNA-mRNA network contained six circRNAs, 30 miRNAs, and 308 mRNAs, and the targeted mRNAs were associated with "regulation of biological process," "intracellular organelle," "protein binding," and enriched in Wnt signaling pathway. Furthermore, qRT-PCR demonstrated that hsa_circRNA_061346, hsa_circRNA_103114, and hsa_circRNA_103870 were significantly up-regulated in GISTs (n = 20), and hsa_ circRNA_405324, hsa_circRNA_406821, and hsa_circRNA_000361 were dramatically down-regulated in GISTs (n = 20). In addition, all of these circRNAs were shown to have high diagnostic values, and most of them were significantly associated with tumor size, mitotic figure, and malignant degrees in GISTs (P < 0.05). Therefore, we concluded that circRNAs were abnormally expressed in GISTs, and the circRNA-miRNA-mRNA regulatory network plays an important role in the occurrence and development of GISTs. Also, the identified six candidate circRNAs might be critical circRNAs and may present as potential diagnostic biomarkers for GISTs.
| S-EPMC7271966 | biostudies-literature
Project description:BackgroundGastric cancer (GC) carries significant morbidity and mortality globally. An increasing number of studies have confirmed that circular RNA (circRNA) is tightly associated with the carcinogenesis and development of GC, especially acting as a competing endogenous RNA for miRNAs.ObjectiveOur study aimed to construct the circRNA-miRNA-mRNA regulatory network and analyze the function and prognostic significance of the network using bioinformatics tools.MethodsWe first downloaded the GC expression profile from the Gene Expression Omnibus database and identified differentially expressed genes and differentially expressed circRNAs. Then, we predicted the miRNA-mRNA interaction pairs and constructed the circRNA-miRNA-mRNA regulatory network. Next, we established a protein-protein interaction network and analyzed the function of these networks. Finally, we primarily validated our results by comparison with The Cancer Genome Atlas cohort and by performing qRT-PCR.ResultsWe screened the top 15 hub genes and 3 core modules. Functional analysis showed that in the upregulated circRNA network, 15 hub genes were correlated with extracellular matrix organization and interaction. The function of downregulated circRNAs converged on physiological functions, such as protein processing, energy metabolism and gastric acid secretion. We ascertained 3 prognostic and immune infiltration-related genes, COL12A1, COL5A2, and THBS1, and built a nomogram for clinical application. We validated the expression level and diagnostic performance of key prognostic differentially expressed genes.ConclusionsIn conclusion, we constructed two circRNA-miRNA-mRNA regulatory networks and identified 3 prognostic and screening biomarkers, COL12A1, COL5A2, and THBS1. The ceRNA network and these genes could play important roles in GC development, diagnosis and prognosis.
| S-EPMC10262520 | biostudies-literature
Project description:BackgroundCircular RNA (circRNA) plays an important role in the regulation of gene expression and the occurrence of human diseases. However, studies on the role of circRNA in acute myocardial infarction (AMI) are limited. This study was performed to explore novel circRNA-related regulatory networks in AMI, aiming to better understand the molecular mechanism of circRNAs involvement in AMI and provide basis for further scientific research and clinical decision-making.MethodsThe AMI-related microarray datasets GSE160717 (circRNA), GSE31568 (miRNA), GSE61741 (miRNA), and GSE24519 (mRNA) were obtained from the Gene Expression Omnibus (GEO) database. After differential expression analysis, the regulatory relationships between these DERNAs were identified by online databases circBank, circInteractome, miRDB, miRWalk, Targetscan, and then two circRNA-miRNA-mRNA regulatory networks were constructed. Differentially expressed genes (DEGs) in this network were selected followed by enrichment analysis and protein-protein interaction (PPI) analysis. Hub genes were identified using Cytohubba plug-in of Cytoscape software. Hub genes and hub gene-related miRNAs were used for receiver operating characteristic curve (ROC) analysis to identify potential biomarkers. The relative expression levels of these biomarkers were further assessed by GSE31568 (miRNA) and GSE66360 (mRNA). Finally, on the basis of the above analysis, myocardial hypoxia model was constructed to verify the expression of Hub genes and related circRNAs.ResultsA total of 83 DEcircRNAs, 109 CoDEmiRNAs and 1204 DEGs were significantly differentially expressed in these datasets. The up-regulated circRNAs and down-regulated circRNAs were used to construct a circRNA-miRNA-mRNA regulatory network respectively. These circRNA-related DEGs were mainly enriched in the terms of "FOXO signaling pathway," "T cell receptor signaling pathway," "MAPK signaling pathway," "Insulin resistance," "cAMP signaling pathway," and "mTOR signaling pathway." The top 10 hub genes ATP2B2, KCNA1, GRIN2A, SCN2B, GPM6A, CACNA1E, HDAC2, SRSF1, ANK2, and HNRNPA2B1 were identified from the PPI network. Hub genes GPM6A, SRSF1, ANK2 and hub gene-related circRNAs hsa_circ_0023461, hsa_circ_0004561, hsa_circ_0001147, hsa_circ_0004771, hsa_circ_0061276, and hsa_circ_0045519 were identified as potential biomarkers in AMI.ConclusionIn this study, the potential circRNAs associated with AMI were identified and two circRNA-miRNA-mRNA regulatory networks were constructed. This study explored the mechanism of circRNA involvement in AMI and provided new clues for the selection of new diagnostic markers and therapeutic targets for AMI.
| S-EPMC9300925 | biostudies-literature
Project description:This study was to identify important circRNA-miRNA-mRNA (ceRNAs) regulatory mechanisms in hepatocellular carcinoma (HCC). The circRNA dataset GSE97332 and miRNA dataset GSE57555 were used for analyses. Functional enrichment analysis for miRNA and target gene was conducted using cluster Profiler. Survival analysis was conducted through R package Survival. The ceRNAs and drug-gene interaction networks were constructed. The ceRNAs network contained five miRNAs including hsa-miR-25-3p, hsa-miR-3692-5p, hsa-miR-4270, hsa-miR-331-3p, and hsa-miR-125a-3p. Among the network, hsa-miR-25-3p targeted the most genes, hsa-miR-3692-5p and hsa-miR-4270 were targeted by more circRNAs than other miRNAs, hsa-circ-0034326 and hsa-circ-0011950 interacted with three miRNAs. Furthermore, target genes, including NRAS, ITGA5, SLC7A1, SEC14L2, SLC12A5, and SMAD2 were obtained in drug-gene interaction network. Survival analysis showed NRAS, ITGA5, SLC7A1, SEC14L2, SLC12A5, and SMAD2 were significantly associated with prognosis of HCC. NRAS, ITGA5, and SMAD2 were significantly enriched in proteoglycans in cancer. Moreover, hsa-circ-0034326 and hsa-circ-0011950 might function as ceRNAs to play key roles in HCC. Furthermore, miR-25-3p, miR-3692-5p, and miR-4270 might be significant for HCC development. NRAS, ITGA5, SEC14L2, SLC12A5, and SMAD2 might be prognostic factors for HCC patients via proteoglycans in cancer pathway. Taken together, the findings will provide novel insight into pathogenesis, selection of therapeutic targets and prognostic factors for HCC.
| S-EPMC8687197 | biostudies-literature
Project description:The pathogenesis of gastric cancer (GC) is still not fully understood. We aimed to find the potential regulatory network for ceRNA (circRNA-miRNA-immune-related mRNA) to uncover the pathological molecular mechanisms of GC. The expression profiles of circRNA, miRNA, and mRNA in gastric tissue from GC patients were downloaded from the Gene Expression Omnibus (GEO) datasets. Differentially expressed circRNAs, miRNAs, and immune-related mRNAs were filtered, followed by the construction of the ceRNA (circRNA-miRNA-immune-related mRNA) network. Functional annotation and protein-protein interaction (PPI) analysis of immune-related mRNAs in the network were performed. Expression validation of circRNAs and immune-related mRNAs was performed in the new GEO and TCGA datasets and in-vitro experiment. A total of 144 differentially expressed circRNAs, 216 differentially expressed miRNAs, and 2,392 differentially expressed mRNAs were identified in GC. Some regulatory pairs of circRNA-miRNA-immune-related mRNA were obtained, including hsa_circ_0050102-hsa-miR-4537-NRAS-Tgd cells, hsa_circ_0001013-hsa-miR-485-3p-MAP2K1-Tgd cells, hsa_circ_0003763-hsa-miR-145-5p-FGF10-StromaScore, hsa_circ_0001789-hsa-miR-1269b-MET-adipocytes, hsa_circ_0040573-hsa-miR-3686-RAC1-Tgd cells, and hsa_circ_0006089-hsa-miR-5584-3p-LYN-neurons. Interestingly, FGF10, MET, NRAS, RAC1, MAP2K1, and LYN had potential diagnostic value for GC patients. In the KEGG analysis, some signaling pathways were identified, such as Rap1 and Ras signaling pathways (involved NRAS and FGF10), Fc gamma R-mediated phagocytosis and cAMP signaling pathway (involved RAC1), proteoglycans in cancer (involved MET), T-cell receptor signaling pathway (involved MAP2K1), and chemokine signaling pathway (involved LYN). The expression validation of hsa_circ_0003763, hsa_circ_0004928, hsa_circ_0040573, FGF10, MET, NRAS, RAC1, MAP2K1, and LYN was consistent with the integrated analysis. In conclusion, the identified ceRNA (circRNA-miRNA-immune-related mRNA) regulatory network may be associated with the development of GC.
| S-EPMC8907717 | biostudies-literature
Project description:BackgroundGPRIN1 may be a novel tumor regulator, but its role and mechanism in tumors are still unclear.MethodsFirst, a pan-cancer correlation analysis was conducted on the expression and prognosis of GPRIN1 based on the data downloaded from The Cancer Genome Atlas (TCGA) database. Second, the Starbase database was used to predict the upstream miRNAs and lncRNAs of GPRIN1, and the expression analysis, survival analysis, and correlation analysis were performed to screen the microRNA (miRNAs)/long non-coding RNAs (lncRNAs) that had a correlation with kidney renal papillary cell carcinoma (KIRP) or lung adenocarcinoma (LUAD). Third, the CIBERSORT algorithm was employed to calculate the proportion of various types of immune cells, and then the R packages were used for evaluating the relation between GPRIN1 expression and tumor immune cell infiltration as well as between GPRIN1 and the immune cell biomarker. Finally, the correlation analysis was made on GPRIN1 and immune checkpoints (CD274, CTLA4, and PDCD1).ResultsThe pan-cancer analysis suggested that GPRIN1 was up-expressed in KIRP and LUAD, and it correlated with poor prognosis. LINC00894/MMP25-AS1/SNHG1/LINC02298/MIR193BHG-miR-140-3p was likely to be the most promising upstream regulation pathway of GPRIN1. Upexpression of LINC00894/MMP25-AS1/SNHG1/LINC02298/MIR193BHG and downexpression of miR-140-3p were found relevant with poor outcomes of KIRP and LUAD. GPRIN1 expression was significantly correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoints.ConclusionsThe competitive endogenous (ceRNA) of miR-140-3p-GPRIN1 axis and its upstream lncRNAs are closely related to KIRP and LUAD, and might affect the prognosis and therapeutic effect of KIRP and LUAD.
| S-EPMC8487820 | biostudies-literature
Project description:BackgroundStroke is the leading cause of death and disability worldwide, with ischemic stroke (IS) being the most prevalent type. Circular RNAs (circRNAs) are involved in the pathological process of IS and are promising biomarkers for the diagnosis of IS. However, studies focusing on circRNAs acting as microRNAs (miRNAs) sponges in regulating mRNA expression are currently scarce.MethodsIn this study, expression profiles of circRNAs (GSE195442), miRNAs (GSE117064), and mRNAs (GSE58294) from the Gene Expression Omnibus (GEO) database were analyzed. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified by R software. The target miRNAs and target genes were predicted by several bioinformatics methods. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEmRNAs. Subsequently, the protein-protein interaction (PPI) network and the competing endogenous RNA (ceRNA) regulatory network were visualized by Cytoscape software. Finally, we further constructed an immune-related circRNA-miRNA-mRNA regulatory sub-network in IS.ResultsA total of 35 DEcircRNAs, 141 DEmiRNAs, and 356 DEmRNAs were identified. By comprehensive analysis of bioinformatics methods, we constructed a circRNA-miRNA-mRNA regulatory network, including 15 DEcircRNAs, eight DEmiRNAs, and 39 DEmRNAs. FGF9 was identified as an immune-related hub gene. Immune cell analysis indicated a significantly higher level of neutrophils in IS, and the expression of FGF9 was significantly negatively correlated with the level of neutrophils. Eventually, miR-767-5p was predicted as the upstream molecules of FGF9, and circ_0127785 and circ_0075008 were predicted as the upstream circRNAs of miR-767-5p.ConclusionOur study provides novel insights into the molecular mechanisms governing the progression of IS from the perspective of immune-related ceRNA networks.
| S-EPMC9240315 | biostudies-literature