Dataset Information

Reconstruction of lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveals functional lncRNAs in skin cutaneous melanoma.

ABSTRACT: BACKGROUND:Human skin cutaneous melanoma is the most common and dangerous skin tumour, but its pathogenesis is still unclear. Although some progress has been made in genetic research, no molecular indicators related to the treatment and prognosis of melanoma have been found. In various diseases, dysregulation of lncRNA is common, but its role has not been fully elucidated. In recent years, the birth of the "competitive endogenous RNA" theory has promoted our understanding of lncRNAs. METHODS:To identify the key lncRNAs in melanoma, we reconstructed a global triple network based on the "competitive endogenous RNA" theory. Gene Ontology and KEGG pathway analysis were performed using DAVID (Database for Annotation, Visualization, and Integration Discovery). Our findings were validated through qRT-PCR assays. Moreover, to determine whether the identified hub gene signature is capable of predicting the survival of cutaneous melanoma patients, a multivariate Cox regression model was performed. RESULTS:According to the "competitive endogenous RNA" theory, 898 differentially expressed mRNAs, 53 differentially expressed lncRNAs and 16 differentially expressed miRNAs were selected to reconstruct the competitive endogenous RNA network. MALAT1, LINC00943, and LINC00261 were selected as hub genes and are responsible for the tumorigenesis and prognosis of cutaneous melanoma. CONCLUSIONS:MALAT1, LINC00943, and LINC00261 may be closely related to tumorigenesis in cutaneous melanoma. In addition, MALAT1 and LINC00943 may be independent risk factors for the prognosis of patients with this condition and might become predictive molecules for the long-term treatment of melanoma and potential therapeutic targets.

SUBMITTER: Zhu J

PROVIDER: S-EPMC7523354 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Reconstruction of lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveals functional lncRNAs in skin cutaneous melanoma.

Zhu Junyou J Deng Jin J Zhang Lijun L Zhao Jingling J Zhou Fei F Liu Ning N Cai Ruizhao R Wu Jun J Shu Bin B Qi Shaohai S

BMC cancer 20200929 1

<h4>Background</h4>Human skin cutaneous melanoma is the most common and dangerous skin tumour, but its pathogenesis is still unclear. Although some progress has been made in genetic research, no molecular indicators related to the treatment and prognosis of melanoma have been found. In various diseases, dysregulation of lncRNA is common, but its role has not been fully elucidated. In recent years, the birth of the "competitive endogenous RNA" theory has promoted our understanding of lncRNAs.<h4> ...[more]

PMID: 32993558

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Project description:ObjectiveSkin cutaneous melanoma(SKCM) is the most severe, and complex disease of all skin cancers. The molecular mechanisms of this cancer progression are not well understood.MethodsGEPIA online database was used to validate the differentially expressed genes from two GEO datasets. The prognostic value was calculated by the Kaplan-Meier method. RT-qPCR verified the expression of TUBB4A in SKCM cell line, and the immunohistochemistry of TUBB4A in SKCM and normal skin tissues were gained from Human Protein Atlas. Seven target prediction databases predicted potential microRNAs(miRNAs), and upstream long non-coding RNAs(lncRNAs) were predicted by starBase. The co-expressed gene of TUBB4A was obtained using the two online analysis sites UALCAN and starBase. These co-expressed genes were performed by enrichment analysis, and immune infiltration result was obtained by the TIMER2 online database. The receiver operating characteristic( ROC) curve was applied to evaluate the diagnostic value of TUBB4A in the SKCM and normal skin group. A new nomogram about TUBB4A was constructed to forecast the survival rate of SKCM patients at 1, 3, and 5 years.ResultsFirstly, we found that DLL3 and TUBB4A were significantly higher expressed in skin cutaneous melanoma than normal skin. Subsequently, by analyzing progress-free interval(PFI), diseasespecific survival(DSS), and disease-free survival(DFS), only TUBB4A was the most potent gene for inhibiting shin cutaneous melanoma progression. In gene ontology(GO)/ kyoto encyclopedia of genes and genomes(KEGG) analysis, TUBB4A may play a key role in the progression of skin cutaneous melanoma by regulating mitochondrial function and affecting cellular metabolism, possibly related to the immune infiltration of CD4+Th1 cells and NK cells. The upstream non-coding RNA(ncRNA) acts through the SNHG16-hsa-let-7b-5p-TUBB4A axis.ConclusionIn conclusion, we elucidated the regulatory role of the SNHG16-hsa-let-7b-5p-TUBB4A axis in the progression of skin cutaneous melanoma by modulating mitochondrial function to affect cellular metabolism. TUBB4A may be a promising diagnostic biomarker and therapeutic target for cutaneous skin melanoma.

Project description:Background The aim of this work was to investigate the competing endogenous RNA (ceRNA) network in adenoid cystic carcinoma of the salivary gland (SACC). Methods Differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) between cancer tissues and normal salivary gland (NSG) in ACC were identified using data from the Gene Expression Omnibus (GEO) database. Functional annotation and pathway enrichment analysis of DEmRNAs were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The miRNAs that are targeted by lncRNAs were predicted using miRanda and PITA, while the target mRNAs of miRNAs were retrieved from miRanda, miRWalk, and TargetScan. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and then we constructed the lncRNA-miRNA-mRNA networks of ACC. Results Differentially expressed RNAs were identified in SACC. Upon comparing cancer tissues and NSG tissues, 103 upregulated and 52 downregulated lncRNAs and 745 upregulated and 866 downregulated mRNAs were identified in GSE88804; in addition, 39 upregulated and 43 downregulated miRNAs were identified in GSE117275. GO enrichment analyses revealed that the most relevant GO terms were regulation of transcription DNA-templated, transcription DNA-templated, and cell division. KEGG pathway enrichment analysis showed that differentially expressed genes (DEGs) were mainly enriched in the cell cycle, pathways in cancer, PI3K-Akt signaling pathway, breast cancer, and microRNAs in cancer. The PPI network consisted of 27 upregulated and 54 downregulated mRNAs. By constructing ceRNA network, NONHSAT251752.1-hsa-miR-6817-5p-NOTCH1, NONHSAT251752.1-hsa-miR-204-5p/hsa-miR-138-5p-CDK6 regulatory axises were identified and all genes in the network were verified by qRT-PCR. Conclusions The present study constructed ceRNA networks in SACC and provided a novel perspective of the molecular mechanisms for SACC.

Project description:Cytogenetically normal acute myeloid leukemia (CN-AML) is a heterogeneous disease with different prognoses. Researches on prognostic biomarkers and therapy targets of CN-AML are still ongoing. Instead of protein-coding genes, more and more researches were focused on the non-coding RNAs especially long non-coding RNAs (lncRNAs) which may play an important role in the development of AML. Although a large number of lncRNAs have been found, our knowledge of their functions and pathological process is still in its infancy. The purpose of this research is to identify the key lncRNAs and explore their functions in CN-AML by reconstructing the lncRNA-miRNA-mRNA network based on the competitive endogenous RNA (ceRNA) theory. We reconstructed a global triple network based on the ceRNA theory using the data from National Center for Biotechnology Information Gene Expression Omnibus and published literature. According to the topological algorithm, we identified the key lncRNAs which had both the higher node degrees and the higher numbers of lncRNA-miRNA pairs and total pairs in the ceRNA network. Meanwhile, Gene Ontology (GO) and pathway analysis were performed using databases such as DAVID, KOBAS and Cytoscape plug-in ClueGO respectively. The lncRNA-miRNA-mRNA network was composed of 90 lncRNAs,33mRNAs,26 miRNAs and 259 edges in the lncRNA upregulated group, and 18 lncRNAs,11 mRNAs,6 miRNAs and 45 edges in the lncRNA downregulated group. The functional assay showed that 53 pathways and 108 GO terms were enriched. Three lncRNAs (XIST, TUG1, GABPB1-AS1) could possibly be selected as key lncRNAs which may play an important role in the development of CN-AML. Particularly, GABPB1-AS1 was highly expressed in CN-AML by both bioinformatic analysis and experimental verification in AML cell line (THP-1) with quantitative real-time polymerase chain reaction. In addition, GABPB1-AS1 was also negatively correlated with overall survival of AML patients. The lncRNA-miRNA-mRNA network revealed key lncRNAs and their functions in CN-AML. Particularly, lncRNA GABPB1-AS1 was firstly proposed in AML. We believe that GABPB1-AS1 is expected to become a candidate prognostic biomarker or a potential therapeutic target.

Project description:BACKGROUND:Acute myeloid leukemia (AML) is one of the most common malignant and aggressive hematologic tumors, and its pathogenesis is associated with abnormal post-transcriptional regulation. Unbalanced competitive endogenous RNA (ceRNA) promotes tumorigenesis and progression, and greatly contributes to tumor risk classification and prognosis. However, the comprehensive analysis of the circular RNA (circRNA)-long non-coding RNA (lncRNA)-miRNA-mRNA ceRNA network in the prognosis of AML is still rarely reported. METHOD:We obtained transcriptome data of AML and normal samples from The Cancer Genome Atlas (TCGA), Genotype-tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases, and identified differentially expressed (DE) mRNAs, lncRNAs, and circRNAs. Then, the targeting relationships among lncRNA-miRNA, circRNA-miRNA, and miRNA-mRNA were predicted, and the survival related hub mRNAs were further screened by univariate and multivariate Cox proportional hazard regression. Finally, the AML prognostic circRNA-lncRNA-miRNA-mRNA ceRNA regulatory network was established. RESULTS:We identified prognostic 6 hub mRNAs (TM6SF1, ZMAT1, MANSC1, PYCARD, SLC38A1, and LRRC4) through Cox regression model, and divided the AML samples into high and low risk groups according to the risk score obtained by multivariate Cox regression. Survival analysis verified that the survival rate of the high-risk group was significantly reduced (p < 0.0001). The prognostic ceRNA network of 6 circRNAs, 32 lncRNAs, 8 miRNAs, and 6 mRNAs was established according to the targeting relationship between 6 hub mRNAs and other RNAs. CONCLUSION:In this study, ceRNA network jointly participated by circRNAs and lncRNAs was established for the first time. It comprehensively elucidated the post-transcriptional regulatory mechanism of AML, and identified novel AML prognostic biomarkers, which has important guiding significance for the clinical diagnosis, treatment, and further scientific research of AML.

Dataset Information

Reconstruction of lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveals functional lncRNAs in skin cutaneous melanoma.

Publications

Reconstruction of lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveals functional lncRNAs in skin cutaneous melanoma.

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