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Construction and Analysis of the Dysregulated ceRNA Network and Identification of Risk Long Noncoding RNAs in Breast Cancer.

ABSTRACT: Breast cancer (BRCA) is the second leading cause of cancer-related mortality in women worldwide. However, the molecular mechanism involved in the development of BRCA is not fully understood. In this study, based on the miRNA-mediated long non-coding RNA (lncRNA)-protein coding gene (PCG) relationship and lncRNA-PCG co-expression information, we constructed and analyzed a specific dysregulated lncRNA-PCG co-expression network in BRCA. Then, we performed the random walk with restart (RWR) method to prioritize BRCA-related lncRNAs through comparing their RWR score and significance. As a result, we identified 30 risk lncRNAs for BRCA, which can distinguish normal and tumor samples. Moreover, through gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, we found that these risk lncRNAs mainly synergistically exerted functions related to cell cycle and DNA separation and replication. At last, we developed a four-lncRNA prognostic signature (including AP000851.1, LINC01977, MAFG-DT, SIAH2-AS1) and assessed the survival accuracy of the signature by performing time-dependent receiver operating characteristic (ROC) analysis. The areas under the ROC curve for 1, 3, 5, and 10 years of survival prediction were 0.68, 0.61, 0.62, and 0.63, respectively. The multivariable Cox regression results verified that the four-lncRNA signature could be used as an independent prognostic biomarker in BRCA. In summary, these results have important reference value for the study of diagnosis, treatment, and prognosis evaluation of BRCA.

SUBMITTER: Su X

PROVIDER: S-EPMC8212960 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Maintenance of the drug-addicted state is thought to involve changes in gene expression in different neuronal cell types and neural circuits. Midbrain dopamine (DA) neurons in particular mediate numerous responses to drugs of abuse. Long noncoding RNAs (lncRNAs) regulate CNS gene expression through a variety of mechanisms, but next to nothing is known about their role in drug abuse. The proportion of lncRNAs that are primate-specific provides a strong rationale for their study in human drug abusers. In this study, we determined a profile of dysregulated putative lncRNAs through the analysis of postmortem human midbrain specimens from chronic cocaine abusers and well-matched control subjects (n = 11 in each group) using a custom lncRNA microarray. A dataset comprising 32 well-annotated lncRNAs with independent evidence of brain expression and robust differential expression in cocaine abusers is presented. For a subset of these lncRNAs, differential expression was validated by quantitative real-time PCR and cellular localization determined by in situ hybridization histochemistry. Examples of lncRNAs exhibiting DA cell-specific expression, different subcellular distributions, and covariance of expression with known cocaine-regulated protein-coding genes were identified. These findings implicate lncRNAs in the cellular responses of human DA neurons to chronic cocaine abuse. Long noncoding RNAs (lncRNAs) regulate the expression of protein-coding genes, but little is known about their potential role in drug abuse. In this study, we identified lncRNAs differentially expressed in human cocaine abusers' midbrains. One up-regulated antisense lncRNA, tumor necrosis factor receptor-associated factor 3-interacting protein 2-antisense 1 (TRAF3IP2-AS1), was found predominantly in the nucleus of human dopamine (DA) neurons, whereas the related TRAF3IP2 protein-coding transcript was distributed throughout these cells. The abundances of these transcripts were significantly correlated (left) suggesting that TRAF3IP2-AS1 may regulate TRAF3IP2 gene expression, perhaps through local chromatin changes at this locus (right).

Project description:Background:Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by chronic progressive stenosis or occlusion of the bilateral internal carotid artery (ICA), the anterior cerebral artery (ACA), and the middle cerebral artery (MCA). MMD is secondary to the formation of an abnormal vascular network at the base of the skull. However, the etiology and pathogenesis of MMD remain poorly understood. Methods:A competing endogenous RNA (ceRNA) network was constructed by analyzing sample-matched messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA) expression profiles from MMD patients and control samples. Then, a protein-protein interaction (PPI) network was constructed to identify crucial genes associated with MMD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were employed with the DAVID database to investigate the underlying functions of differentially expressed mRNAs (DEmRNAs) involved in the ceRNA network. CMap was used to identify potential small drug molecules. Results:A total of 94 miRNAs, 3649 lncRNAs, and 2294 mRNAs were differentially expressed between MMD patients and control samples. A synergistic ceRNA lncRNA-miRNA-mRNA regulatory network was constructed. Core regulatory miRNAs (miR-107 and miR-423-5p) and key mRNAs (STAT5B, FOSL2, CEBPB, and CXCL16) involved in the ceRNA network were identified. GO and KEGG analyses indicated that the DEmRNAs were involved in the regulation of the immune system and inflammation in MMD. Finally, two potential small molecule drugs, CAY-10415 and indirubin, were identified by CMap as candidate drugs for treating MMD. Conclusions:The present study used bioinformatics analysis of candidate RNAs to identify a series of clearly altered miRNAs, lncRNAs, and mRNAs involved in MMD. Furthermore, a ceRNA lncRNA-miRNA-mRNA regulatory network was constructed, which provides insights into the novel molecular pathogenesis of MMD, thus giving promising clues for clinical therapy.

Project description:PurposeExosomes are able to exchange their bioactive RNA cargo to recipient cells. In COPD, exosomes can be controlled and engineered for its use as targeted diagnostic and therapeutic tool. Our study explored novel lncRNAs and mRNAs in plasma exosomes that could be involved in the pathogenesis of COPD.MethodsHigh-throughput sequencing was conducted to detect the alterations in the expression of exosomal lncRNAs and mRNAs. Gene ontology (GO) functional analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to determine the significant functions and pathways associated with differentially expressed (DE) lncRNAs. The mRNA expression profile dataset, GSE76925, and microRNA expression profile dataset, GSE70080, were obtained from the GEO database. Venn diagrams were used to find common DE mRNAs between my mRNAs dataset and GSE76925. These common DEGs were subjected to PPI analyses to identify Hub genes. Subsequently, Venn diagrams were used to identify common genes between the target genes of DE-miRNAs and Hub genes as well as DE-miRNAs and my lncRNAs dataset. Finally, a lncRNA-miRNA-mRNA co-expression network was constructed by prediction using proprietary software. The lncRNA and mRNA expressions were then validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR).ResultsWe identified 1578 differentially regulated lncRNAs and 3071 differentially regulated mRNAs. GO and KEGG pathway analyses suggested that the DE lncRNAs are involved in the pathogenesis of COPD. A lncRNA-miRNA-mRNA meshwork was established to predict the potential interactions among these RNAs. RP3-329A5.8 and MRPS11 expression was then subjected to qRT-PCR for validation. Correlations between MRPS11 and clinic-pathological features were explored.ConclusionOur study provided a set of lncRNAs and mRNAs that may be involved in the pathogenesis of COPD, thereby highlighting the need for further research on both diagnostic biomarkers and molecular mechanisms.

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Construction and Analysis of the Dysregulated ceRNA Network and Identification of Risk Long Noncoding RNAs in Breast Cancer.

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