Comprehensive analysis of long non?coding RNA using an associated competitive endogenous RNA network in Wilms tumor.
ABSTRACT: Wilms tumor (WT) is the most common malignant renal neoplasm in children; however, the underlying molecular mechanisms are not well understood. According to the competing endogenous RNA (ceRNA) theory, long non?coding RNAs (lncRNAs) can regulate the expression of target genes by adsorbing microRNAs (miRNAs/miRs). However, the role of lncRNAs in WT has not been fully elucidated. The aim of the present study was to construct a ceRNA network to identify the potential lncRNAs involved in WT. The expression profiles of lncRNAs, miRNAs and mRNAs in 120 WT and six normal tissues were obtained from the Therapeutically Applicable Research to Generate Effective Treatments database. A total of 442 lncRNAs, 214 miRNAs and 4,912 mRNAs were identified as differentially expressed in WT and were enriched in 472 Gene Ontology terms (355 biological processes, 89 cellular components and 29 molecular functions) and 18 Kyoto Encyclopedia of Genes and Genomes pathways. A lncRNA?miRNA?mRNA ceRNA network of WT consisting of with 32 lncRNAs, 14 miRNAs and 158 mRNAs was constructed, based on the bioinformatics analysis of the miR target prediction database and the miRNAcode, miRTarBase and TargetScan databases. Subsequently, three lncRNAs, three miRNAs and 17 mRNAs, which had a significant effect on the overall survival rate of patients with WT, were identified based on the survival analysis. The three lncRNAs were also differentially expressed in the late and early stages of WT and were validated using the GSE66405 dataset obtained from the Gene Expression Omnibus database. In conclusion, the present study generated a specific lncRNA?related ceRNA network of WT, which may provide a novel perspective on the molecular mechanisms underlying the progression and prognosis of the disease.
Project description:Long noncoding RNA (lncRNA) plays crucial roles in various biological processes of different cancers, especially acting as a competing endogenous RNA (ceRNA). However, the role of lncRNA-mediated ceRNA in Wilms tumor (WT), which is the most common malignant kidney cancer in children, remains unknown. In present study, RNA sequence profiles and clinical data of 125 patients with WT consisting of 119 tumor and 6 normal tissues from Therapeutically Applicable Research To Generate Effective Treatments database were analyzed. A total of 1833 lncRNAs, 156 microRNAs (miRNAs), and 3443 messenger RNAs (mRNAs) were identified as differentially expressed (DE) using "DESeq2" package. The lncRNA-miRNA-mRNA ceRNA regulatory network involving 748 DElncRNAs, 33 DEmiRNAs, and 189 DEmRNAs was constructed based on miRcode, Targetscan, miRTarBase, and miRDB database. Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that DEmRNAs were mainly enriched in cell proliferation-related processes and tumor-related pathways, respectively, and 13 hub genes were identified by a protein-protein interaction network. Survival analysis detected 48 lncRNAs, 7 miRNAs, and 16 mRNAs to have significant impact on the overall survival of patients with WT. Additionally, we found that 6 DElncRNAs with potential prognostic value were correlated with tumor stage (DENND5B-AS1) and histologic classification (TMPO-AS1, RP3-523K23.2, RP11-598F7.3, LAMP5-AS1, and AC013275.2) of patients with WT. Our research provides a great insight into understanding the molecular mechanism underlying occurrence and progression of WT, as well as the potential to develop targeted therapies and prognostic biomarkers.
Project description:BACKGROUND Long noncoding RNAs (lncRNAs) have been revealed to function as competing endogenous RNAs (ceRNAs), which can seclude the common microRNAs (miRNAs) and hence prevent the miRNAs from binding to their ancestral gene. Nonetheless, the role of lncRNA-mediated ceRNAs in prostate cancer has not yet been elucidated. MATERIAL AND METHODS Using The Cancer Genome Atlas (TCGA) database, lncRNA, miRNA, and mRNA profiles from 499 prostate cancer tissues and 52 normal prostate tissues were analyzed with the R package "DESeq" to identify the differentially expressed RNAs. GO and KEGG pathway analyses were performed using "DAVID6.8" and R packages "Clusterprofile." The ceRNA network in prostate cancer was constructed using miRDB, miRTarBase, and TargetScan databases. Survival analysis was performed with Kaplan-Meier analysis. RESULTS A total of 376 lncRNAs, 33 miRNAs, and 687 mRNAs were identified as significant factors in tumorigenesis. Based on the hypothesis that the ceRNA network (lncRNA-miRNA-mRNA regulatory axis) is involved in prostate cancer and forms competitive interrelations between miRNA and mRNA or lncRNA, we constructed a ceRNA network that included 23 lncRNAs, 6 miRNAs, and 2 mRNAs that were differentially expressed in prostate cancer. Only 3 lncRNAs (LINC00308, LINC00355, and OSTN-AS1) had a significant association with survival (P<0.05). The 3 prostate cancer-specific lncRNA were validated in prostate cancer cell lines PC3 and DU145 using qRT-PCR. CONCLUSIONS We demonstrated the differential lncRNA expression profiles in prostate cancer, which provides new insights for future studies of the ceRNA network and its regulatory mechanisms in prostate cancer.
Project description:BACKGROUND The aim of this study was to analyze the long non-coding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network in human retinal tissues following detachment with proliferative vitreoretinopathy (PVR). MATERIAL AND METHODS Expression data of 19 human detached retinas with PVR and 19 normal retinas from postmortem donors were downloaded from Gene Expression Omnibust (GEO) database (GSE28133). The R package "limma" was utilized to discriminate the dysregulated lncRNA and mRNA profiles. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of differentially expressed mRNAs were performed using R packages "Clusterprofiler." The ceRNA network of dysregulated genes was constructed by using mircode, miRDB, miRTarBase and TargetScan databases, and was visualized by Cytoscape v3.6.1. RESULTS A total of 23 lncRNAs and 994 mRNAs were identified significantly expressed between the human detached retinas with PVR and the normal retina tissues, with thresholds of |log?FoldChange| >1.0 and adjusted P-value <0.05. The constructed ceRNA network (lncRNA-miRNA-mRNA regulatory axis) included 9 PVR-specific lncRNAs, as well as 27 miRNAs and 73 mRNAs. CONCLUSIONS We demonstrated the di?erential lncRNA expression profile and constructed a lncRNA-associated ceRNA network in human detached retinas with PVR. This may ferret out an unknown ceRNA regulatory network in human retinal detachment with PVR.
Project description:Long non-coding RNA (lncRNA) is a kind of non-coding RNA with transcripts more than 200 bp in length. LncRNA can interact with the miRNA as a competing endogenous RNA (ceRNA) to regulate the expression of target genes, which play a significant role in the initiation and progression of tumors. In this study, we explored the functional roles and regulatory mechanisms of lncRNAs as ceRNAs in gastric cancer, and their potential implications for prognosis. The lncRNAs, miRNAs, and mRNAs expression profiles of 375 gastric cancer tissues and 32 non-tumor gastric tissues were downloaded from The Cancer Genome Atlas (TCGA) database. Differential expression of RNAs was identified using the DESeq package. Survival analysis was estimated based on Kaplan-Meier curve analysis. KEGG pathway analysis was performed using KOBAS 3.0. The dysregulated lncRNA-associated ceRNA network was constructed in gastric cancer based on bioinformatics generated from miRcode and miRTarBase. A total of 237 differentially expressed lncRNAs and 198 miRNAs between gastric cancer and matched normal tissues were screened in our study with thresholds of |log2FC| >2 and adjusted P value <0.01. Eleven discriminatively expressed lncRNAs may be correlated with tumorigenesis of gastric cancer. Seven out of 11 dysregulated lncRNA were found to be significantly associated with overall survival in gastric cancer (P value <0.05). The newly identified ceRNA network includes 11 gastric cancer-specific lncRNAs, 9 miRNAs, and 41 mRNAs. Collectively, our study will contribute to improving the understanding of the lncRNA-associated ceRNA network regulatory mechanisms in the pathogenesis of gastric cancer and provide and identify novel lncRNAs as candidate prognostic biomarkers or potential therapeutic targets.
Project description:Cholangiocarcinoma (CCA) is the second widespread liver tumor with relatively poor survival. Increasing evidence in recent studies showed long noncoding RNAs (lncRNAs) exert a crucial impact on the development and progression of CCA based on the mechanism of competing endogenous RNAs (ceRNAs). However, functional roles and regulatory mechanisms of lncRNA-regulated ceRNA in CCA, are only partially understood. The expression profile of messenger RNAs (mRNAs), lncRNAs, and microRNAs (miRNAs) downloaded from The Cancer Genome Atlas were comprehensively investigated. Differential expression of these three types of RNA between CCA and corresponding precancerous tissues were screened out for further analysis. On the basis of interactive information generated from miRDB, miRTarBase, TargetScan, and miRcode public databases, we then constructed an mRNA-miRNA-lncRNA regulatory network. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were conducted to identify the biological function of the ceRNA network involved in CCA. As a result, 2883 mRNAs, 136 miRNAs, and 993 lncRNAs were screened out as differentially expressed RNAs in CCA. In addition, a ceRNA network in CCA was constructed, composing of 50 up and 27 downregulated lncRNAs, 14 up and 7 downregulated miRNAs, 29 up and 25 downregulated mRNAs. Finally, gene set enrichment and pathway analysis indicated our CCA-specific ceRNA network was related with cancer-related pathway and molecular function. In conclusion, our research identified a novel lncRNA-related ceRNA network in CCA, which might act as a potential therapeutic target for patients with CCA.
Project description:Long non?coding RNAs (lncRNAs) are a group of non?coding transcripts of >200 nucleotides. They can act as competing endogenous RNAs (ceRNAs) and suppress microRNA (miRNA) function by preventing them from binding to and interacting with target mRNAs. However, the specific role of the lncRNA?associated ceRNA network in the pathogenesis of glaucoma has not yet been elucidated. To study this, data were downloaded from the Gene Expression Omnibus database (GSE126170), which contained three human trabecular meshwork cell (HTMC) samples treated with 300 µm hydrogen peroxide and three control samples treated with vehicle. Differentially expressed lncRNAs and mRNAs of HTMCs were obtained using the R package limma. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of differentially expressed mRNAs were performed using the R package clusterProfiler. Finally, the ceRNA network was constructed using the mircode, miRDB, miRTarBase and TargetScan databases, and visualized using Cytoscape v3.6.1. The results showed that 70 lncRNAs and 558 mRNAs were identified to be significantly dysregulated (|log2FoldChange| >1 and adjusted P<0.05) in HTMCs under oxidative stress compared to those in HTMCs under control conditions. Moreover, 24 lncRNAs, 24 miRNAs and 40 mRNAs were closely connected, and were part of the ceRNA network. Among these, the expression levels of 19 lncRNAs were upregulated, and those of 5 lncRNAs were downregulated. To conclude, using bioinformatics analysis, the differential expression profiles of lncRNAs were reported and a lncRNA?associated ceRNA network in HTMCs under oxidative stress was constructed. These results may bring to light a new pathological mechanism or a potential therapeutic target for glaucoma.
Project description:Background and Objective: Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional deformity of the spine. Mesenchymal stem cells (MSCs) regulate bone mass homeostasis in AIS, which might be related to the pathogenesis of AIS. However, the mRNA-miRNA-lncRNA network linked to the regulation of the genetic pathogenesis of MSCs remains unknown. Methods: We conducted an exhaustive literature search of PubMed, EMBASE, and the Gene Expression Omnibus database to find differentially expressed genes (DEGs), differentially expressed miRNAs (DE miRNAs), and differentially expressed lncRNAs (DE lncRNAs). Functional enrichment analysis was performed through Enrichr database. Protein-protein interaction (PPI) network was constructed using STRING database, and hub genes were identified by CytoHubba. Potential regulatory miRNAs and lncRNAs of mRNAs were predicted by miRTarBase and RNA22, respectively. Results: We identified 551 upregulated and 476 downregulated genes, 42 upregulated and 12 downregulated miRNAs, and 345 upregulated and 313 downregulated lncRNAs as DEGs, DE miRNAs, and DE lncRNAs, respectively. Functional enrichment analysis revealed that they were significantly enriched in protein deglutamylation and regulation of endoplasmic reticulum unfolded protein response. According to node degree, one upregulated hub gene and eight downregulated hub genes were identified. After drawing the Venn diagrams and matching to Cytoscape, an mRNA-miRNA-lncRNA network linked to the pathogenesis of MSCs in AIS was constructed. Conclusion: We established a novel triple regulatory network of mRNA-miRNA-lncRNA ceRNA, among which all RNAs may be utilized as the pathogenesis biomarker of MSCs in AIS.
Project description:Previous studies have emphasized the significant functions of long non-coding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in tumor biology. However, the functions of certain cancer lncRNAs in the lncRNA-related ceRNA network in lung adenocarcinoma (LUAD) are unknown. A systematic and integrative survey of RNA-seq data from The Cancer Genome Atlas (TCGA) was performed to identify candidate lncRNAs for the prognosis of LUAD. In total, 20,502 genes that contain 181 lncRNAs were evaluated in a cohort of 570 LUAD cases. Initially, 6,280 differentially expressed genes (fold-change >2, P<0.05) were obtained using R package, which includes 75 lncRNAs. Next, by univariate regression and multivariate Cox proportional hazards analysis, 32 genes were associated with survival in LUAD. Using these 29 mRNAs and 3 lncRNAs, a prognosis index (PI) was calculated to accurately estimate the survival in LUAD: PI=?exprisk gene × HRrisk gene. Furthermore, the 32-gene signature was an independent prognostic indicator for LUAD (HR >1; P<0.05, by multivariate analysis). Weighted gene co-expression network analysis (WGCNA) of three risk lncRNAs-FAM138B, NHEG1 and TLX1NB-was performed, based on the P-values of the associated genes, and the top 27 miRNAs that bound to these lncRNAs were predicted by Miranda as target miRNAs. Next, these target miRNAs were transferred to the TarBase, miRTarBase, miRecards and starBase v2.0 databases to obtain their target genes. According to the previous miRNA-mRNA and miRNA-lncRNA data, three lncRNA-miRNA-mRNA ceRNA networks were established, based on the 29 prognostic mRNAs, forming a regulatory network in LUAD. The present study provided insight into the lncRNA-related ceRNA network in LUAD and has identified potential diagnostic and prognostic biomarkers.
Project description:BackgroundThe aim of this study was to investigate the regulatory network of lncRNAs as competing endogenous RNAs (ceRNA) in bladder urothelial carcinoma (BUC) based on gene expression data derived from The Cancer Genome Atlas (TCGA).Materials and methodsRNA sequence profiles and clinical information from 414 BUC tissues and 19 non-tumor adjacent tissues were downloaded from TCGA. Differentially expressed RNAs derived from BUC and non-tumor adjacent samples were identified using the R package “edgeR”. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using the “clusterProfiler” package. Gene ontology and protein–protein interaction (PPI) networks were analyzed for the differentially expressed mRNAs using the “STRING” database. The network for the dysregulated lncRNA associated ceRNAs was then constructed for BUC using miRcode, miRTarBase, miRDB, and TargetScan. Cox regression analysis was performed to identify independent prognostic RNAs associated with BUC overall survival (OS). Survival analysis for the independent prognostic RNAs within the ceRNA network was calculated using Kaplan–Meier curves.ResultsBased on our analysis, a total of 666, 1819 and 157 differentially expressed lncRNAs, mRNAs and miRNAs were identified respectively. The ceRNA network was then constructed and contained 59 lncRNAs, 23 DEmiRNAs, and 52 DEmRNAs. In total, 5 lncRNAs (HCG22, ADAMTS9-AS1, ADAMTS9-AS2, AC078778.1, and AC112721.1), 2 miRNAs (hsa-mir-145 and hsa-mir-141) and 6 mRNAs (ZEB1, TMEM100, MAP1B, DUSP2, JUN, and AIFM3) were found to be related to OS. Two lncRNAs (ADAMTS9-AS1 and ADAMTS9-AS2) and 4 mRNA (DUSP2, JUN, MAP1B, and TMEM100) were validated using GEPIA. Thirty key hub genes were identified using the ranking method of degree. KEGG analysis demonstrated that the majority of the DEmRNAs were involved in pathways associated with cancer.ConclusionOur findings provide an understanding of the important role of lncRNA–related ceRNAs in BUC. Additional experimental and clinical validations are required to support our findings.
Project description:long noncoding RNAs (lncRNAs) play crucial roles in regulating gene expression by acting as competing endogenous RNAs (ceRNAs). Overall design: Based on high throughput sequencing data of RPE cells treated by clusterin or not, we first identified differentially expressed mRNAs, lncRNAs and miRNAs. Then, we constructed an lncRNA-mRNA-miRNA network (ceRNA network) based on bioinformatic database miRanda and microRNA (miRNA) targets database miRTarBase.