Identification of prognostic long intergenic non-coding RNAs as competing endogenous RNAs with KRAS mutations in colorectal cancer.
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ABSTRACT:
SUBMITTER: Xu J
PROVIDER: S-EPMC8371979 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Long intergenic non-coding RNAs (lincRNAs) may play widespread roles in gene regulation and other biological processes, however, a systematic examination of the functions of lincRNAs in the biological responses of rice to phosphate (Pi) starvation has not been performed. Here, we used a computational method to predict the functions of lincRNAs in Pi-starved rice. Overall, 3,170 lincRNA loci were identified using RNA sequencing data from the roots and shoots of control and Pi-starved rice. A competing endogenous RNA (ceRNA) network was constructed for each tissue by considering the competing relationships between lincRNAs and genes, and the correlations between the expression levels of RNAs in ceRNA pairs. Enrichment analyses showed that most of the communities in the networks were related to the biological processes of Pi starvation. The lincRNAs in the two tissues were individually functionally annotated based on the ceRNA networks, and the differentially expressed lincRNAs were biologically meaningful. For example, XLOC_026030 was upregulated from 3 days after Pi starvation, and its functional annotation was 'cellular response to Pi starvation'. In conclusion, we systematically annotated lincRNAs in rice and identified those involved in the biological response to Pi starvation.
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Project description:MicroRNAs (miRNAs), a class of small non-coding RNA molecules, are responsible for RNA silencing and post-transcriptional regulation of gene expression. They can mediate a fine-tuned crosstalk among coding and non-coding RNA molecules sharing miRNA response elements (MREs). In a suitable environment, both coding and non-coding RNA molecules can be targeted by the same miRNAs and can indirectly regulate each other by competing for them. These RNAs, otherwise known as competing endogenous RNAs (ceRNAs), lead to an additional post-transcriptional regulatory layer, where non-coding RNAs can find new significance. The miRNA-mediated interplay among different types of RNA molecules has been observed in many different contexts. The analyses of ceRNA networks in cancer and other pathologies, as well as in other physiological conditions, provide new opportunities for interpreting omics data for the field of personalized medicine. The development of novel computational tools, providing putative predictions of ceRNA interactions, is a rapidly growing field of interest. In this review, I discuss and present the current knowledge of the ceRNA mechanism and its implications in a broad spectrum of different pathologies, such as cardiovascular or autoimmune diseases, cancers and neurodegenerative disorders.
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Project description:Long non?coding RNAs (lncRNAs) represent potential biomarkers for the diagnosis and treatment of various diseases; however, the role of circulating acute ischemic stroke (AIS)?related lncRNAs remains relatively unknown. The present study aimed to screen crucial lncRNAs for AIS based on the competing endogenous RNA (ceRNA) hypothesis. The expression profile datasets for one mRNA, accession no. GSE16561, and four microRNAs (miRNAs), accession nos. GSE95204, GSE86291, GSE55937 and GSE110993, were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs), lncRNAs (DELs), and miRNAs (DEMs) were identified, and ClusterProfiler was used to interpret the function of the DEGs. Based on the protein?protein interaction (PPI) network and module analyses, hub DEGs were identified. A ceRNA network was established based on miRNA?mRNA or miRNA?lncRNA interaction pairs. In total, 2,041 DEGs and 5 DELs were identified between the AIS and controls samples in GSE16561, and 10 DEMs between at least two of the four miRNA expression profiles. A PPI network was constructed with 1,235 DEGs, among which 20 genes were suggested to be hub genes. The hub genes paxillin (PXN), FYN?proto?oncogene, Src family tyrosine kinase (FYN), ras homolog family member A (RHOA), STAT1, and growth factor receptor?bound protein 2 (GRB2), were amongst the most significantly enriched modules extracted from the PPI network. Functional analysis revealed that these hub genes were associated with inflammation?related signaling pathways. An AIS?related ceRNA network was constructed, in which 4 DELs were predicted to function as ceRNAs for 9 DEMs, to regulate the five identified hub genes; that is, minichromosome maintenance complex component 3 associated protein?antisense RNA 1 (MCM3AP?AS1)/long intergenic non?protein coding RNA 1089 (LINC01089)/hsa?miRNA (miR)?125a/FYN, inositol?tetrakisphosphate 1?kinase?antisense RNA 1 (ITPK1?AS1)/hsa?let?7i/RHOA/GRB2/STAT1, and human leukocyte antigen complex group 27 (HCG27)/hsa?-miR?19a/PXN interaction axes. In conclusion, MCM3AP?AS1, LINC01089, ITPK1?AS1, and HCG27 may represent new biomarkers and underlying targets for the treatment of AIS.
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Project description:Gastric cancer (GC) is one of the most frequently occurring life-threatening malignancies worldwide. Due to its high mortality rate, the discovery of putative biomarkers that may be sensitive and specific to GC is of seminal importance. Long non-coding RNAs (lncRNAs) are non-translatable RNAs whose transcript length exceeds 200 base pairs. The dysregulation of lncRNA expression plays a key role in tumorigenesis and development. In the present study, the expression profiles of lncRNAs, microRNAs and mRNAs of 361 GC tissues (and 32 normal gastric tissues) were downloaded from The Cancer Genome Atlas database. Furthermore, differentially expressed RNAs were analyzed by the DEseq package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses confirmed some significant dysregulated signaling pathways and target RNAs. As a result, an lncRNA-associated competing endogenous RNA (ceRNA) network was constructed. Kaplan-Meier analysis of the differentially expressed RNAs associated with GC pathogenesis confirmed that the lncRNAs PVT1, HAND2-AS1 and ZNF667-AS1 were potentially associated with the prognosis of GC (P<0.05). The present study suggests the mechanism of ceRNA networks in GC, and further demonstrates that aberrant lncRNA expression may be used as an effective diagnostic tool (or target) for the prognosis of GC.
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Project description:The discovery that the mammalian transcriptome encodes thousands of long intergenic non-coding (linc) RNA transcripts, together with recent evidence that lincRNAs can regulate protein-coding genes, has added a new level of complexity to cellular transcriptional/translational regulation. Indeed several reports now link mutations in lincRNAs to heritable human disorders. Here, we identified a subset of lincRNAs in terminally differentiated adult human retinal neurons based on their sequence conservation across species. RNA sequencing of eye tissue from several mammalian species with varied rod/cone photoreceptor content identified 18 lincRNAs that were highly conserved across these species. Sixteen of the 18 were conserved in human retinal tissue with 14 of these also conserved in the macular region. A subset of lincRNAs exhibited restricted tissue expression profiles in mice, with preferential expression in the retina. Mouse models with different populations of retinal cells as well as in situ hybridization provided evidence that these lincRNAs localized to specific retinal compartments, most notably to the photoreceptor neuronal layer. Computational genomic loci and promoter region analyses provided a basis for regulated expression of these conserved lincRNAs in retinal post-mitotic neurons. This combined approach identified several lincRNAs that could be critical for retinal and visual maintenance in adults.
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Project description:Some long noncoding RNAs (lncRNAs) play important roles in the regulation of gene expression by acting as competing endogenous RNAs (ceRNAs). However, the roles of lncRNA associated-ceRNAs in oncogenesis are not fully understood. Here, based on lncRNA microarray data of gastric cancer, bioinformatic algorithm miRcode and microRNA (miRNA) targets database TarBase, we first constructed an lncRNA-miRNA-mRNA network. Then, we confirmed it by data of six types of other cancer including head and neck squamous cell carcinoma, prostate cancer, papillary thyroid carcinoma, pituitary gonadotrope tumors, ovarian cancer, and chronic lymphocytic leukemia. The results showed a clear cancer-associated ceRNA network. Eight lncRNAs (AC009499.1, GACAT1, GACAT3, H19, LINC00152, AP000288.2, FER1L4, and RP4-620F22.3) and nine miRNAs (miR-18a-5p, miR-18b-5p, miR-19a-3p, miR-20b-5p, miR-106a-5p, miR-106b-5p, miR-31-5p, miR-139-5p, and miR-195-5p) were involved. For instance, through its miRNA response elements (MREs) to compete for miR-106a-5p, lncRNA-FER1L4 regulates the expression of PTEN, RB1, RUNX1, VEGFA, CDKN1A, E2F1, HIPK3, IL-10, and PAK7. Furthermore, cellular experimental results indicated that FER1L4-small interfering RNA (siRNA) simultaneously suppressed FER1L4 and RB1 mRNA level. These results suggest that lncRNAs harbor MREs and play important roles in post-transcriptional regulation in cancer.
| S-EPMC4133709 | biostudies-literature
Project description:BACKGROUND:Asthma is a heterogeneous disease characterized by chronic airway inflammation. Long non-coding RNA can act as competing endogenous RNA to mRNA, and play significant role in many diseases. However, there is little known about the profiles of long non-coding RNA and the long non-coding RNA related competing endogenous RNA network in asthma. In current study, we aimed to explore the long non-coding RNA-microRNA-mRNA competing endogenous RNA network in asthma and their potential implications for therapy and prognosis. METHODS:Asthma-related gene expression profiles were downloaded from the Gene Expression Omnibus database, re-annotated with these genes and identified for asthma-associated differentially expressed mRNAs and long non-coding RNAs. The long non-coding RNA-miRNA interaction data and mRNA-miRNA interaction data were downloaded using the starBase database to construct a long non-coding RNA-miRNA-mRNA global competing endogenous RNA network and extract asthma-related differentially expressed competing endogenous RNA network. Finally, functional enrichment analysis and drug repositioning of asthma-associated differentially expressed competing endogenous RNA networks were performed to further identify key long non-coding RNAs and potential therapeutics associated with asthma. RESULTS:This study constructed an asthma-associated competing endogenous RNA network, determined 5 key long non-coding RNAs (MALAT1, MIR17HG, CASC2, MAGI2-AS3, DAPK1-IT1) and identified 8 potential new drugs (Tamoxifen, Ruxolitinib, Tretinoin, Quercetin, Dasatinib, Levocarnitine, Niflumic Acid, Glyburide). CONCLUSIONS:The results suggested that long non-coding RNA played an important role in asthma, and these novel long non-coding RNAs could be potential therapeutic target and prognostic biomarkers. At the same time, potential new drugs for asthma treatment have been discovered through drug repositioning techniques, providing a new direction for the treatment of asthma.
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Project description:BackgroundAccumulating evidence has revealed that long non-coding RNAs (lncRNAs) play vital roles in the progression of non-small cell lung cancer (NSCLC). But the relationship between lncRNAs and survival outcome of NSCLC remains to be explored. Therefore, we attempt to figure out their survival roles and molecular connection in NSCLC.MethodsBy analyzing the transcriptome profiling of NSCLC from TCGA databases, we divided patients into three groups, and identified differentially expressed lncRNAs (DELs) of each group. Next, we explored the prognostic roles of common DELs by univariate and multivariate Cox analysis, Lasson, and Kaplan-Meier analysis. Additionally, we assessed and compared the prognostic accuracy of 5 lncRNAs through ROC curves and AUC values. Ultimately, we detected their potential function by enrichment analysis and molecular connection through establishing a competing endogenous RNA (ceRNA) network.ResultsOne hundred ninety-seven common DELs were spotted. And we successfully screened out 5 lncRNAs related to the patient's survival, including LINC01833, AC112206.2, FAM83A-AS1, BANCR, and HOTAIR. Combing with age and AJCC stage, we constructed a nomogram that prognostic prediction was superior to the traditional parameters. Furthermore, 275 qualified mRNAs related to 5 lncRNAs were spotted. Functional analysis indicates that these lncRNAs act key roles in the progression of NSCLC, such as P53 and cell cycle signaling pathway. And ceRNA network also suggests that these lncRNAs are tightly connected with tumor progression.ConclusionsA nomogram and ceRNA network based on 5 lncRNAs indicate that there can effectively predict the overall survival of NSCLC and potentially serve as a therapeutic guide for NSCLC.
| S-EPMC8067646 | biostudies-literature
Project description:Eukaryotic genomes express numerous long intergenic non-coding RNAs (lincRNAs) that do not overlap any coding genes. Some lincRNAs function in various aspects of gene regulation, but it is not clear in general to what extent lincRNAs contribute to the information flow from genotype to phenotype. To explore this question, we systematically analysed cellular roles of lincRNAs in Schizosaccharomyces pombe. Using seamless CRISPR/Cas9-based genome editing, we deleted 141 lincRNA genes to broadly phenotype these mutants, together with 238 diverse coding-gene mutants for functional context. We applied high-throughput colony-based assays to determine mutant growth and viability in benign conditions and in response to 145 different nutrient, drug, and stress conditions. These analyses uncovered phenotypes for 47.5% of the lincRNAs and 96% of the protein-coding genes. For 110 lincRNA mutants, we also performed high-throughput microscopy and flow cytometry assays, linking 37% of these lincRNAs with cell-size and/or cell-cycle control. With all assays combined, we detected phenotypes for 84 (59.6%) of all lincRNA deletion mutants tested. For complementary functional inference, we analysed colony growth of strains ectopically overexpressing 113 lincRNA genes under 47 different conditions. Of these overexpression strains, 102 (90.3%) showed altered growth under certain conditions. Clustering analyses provided further functional clues and relationships for some of the lincRNAs. These rich phenomics datasets associate lincRNA mutants with hundreds of phenotypes, indicating that most of the lincRNAs analysed exert cellular functions in specific environmental or physiological contexts. This study provides groundwork to further dissect the roles of these lincRNAs in the relevant conditions.
| S-EPMC8730722 | biostudies-literature
Project description:ObjectiveTo identify male infertility-related long non-coding (lnc)RNAs and an lncRNA-related competing endogenous (ce)RNA network.MethodsExpression data including 13 normospermic and eight teratozoospermic samples from postmortem donors were downloaded from the GEO database (GSE6872). The limma R package was used to discriminate dysregulated lncRNA and micro (m)RNA profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of differentially expressed (DE) mRNAs were performed using the clusterProfiler R package. The ceRNA network of dysregulated genes was visualized by Cytoscape.ResultsA total of 101 DE lncRNAs and 1722 mRNAs were identified as male infertility-specific RNAs with thresholds of |log2FoldChange| >2.0 and adjusted P-value <0.05. GO and KEGG pathways were analyzed for DE mRNAs. Gene set enrichment analysis revealed that DE genes were enriched in embryonic skeletal system development and cytokine-cytokine receptor interactions. A ceRNA network was constructed with 26 key lncRNAs, 33 microRNAs, and 133 mRNAs. DE lncRNAs in male sterility were mainly associated with transferring phosphorus-containing groups and complexes of histone methyltransferases, methyltransferases, PcG proteins, and serine/threonine protein kinases.ConclusionThis provides a novel perspective to study lncRNA-related ceRNA networks in male infertility and assist in identifying new potential biomarkers for diagnostic purposes.
| S-EPMC7580164 | biostudies-literature