Dataset Information

The mRNA, miRNA and lncRNA networks in hepatocellular carcinoma: An integrative transcriptomic analysis from Gene Expression Omnibus.

ABSTRACT: Research advances and analysis in the non?protein coding part of the human genome have suggested that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are associated with tumor initiation, growth and metastasis. Accumulating studies have demonstrated that a class of miRNAs and lncRNAs are dysregulated in hepatocellular carcinoma (HCC) and closely associated with tumorigenesis, diagnosis and prognosis. In the present study, integrative analysis of published data on multi?level Gene Expression Omnibus (GEO) and a bioinformatics computational approach were used to predict regulatory mechanism networks among differentially expressed mRNAs, miRNAs, and lncRNAs. Firstly, nine microarray expression data sets of mRNAs, miRNAs, and lncRNAs associated with HCC were collected from GEO datasets. Secondly, a total of 628 mRNAs, 15 miRNAs, and 49 lncRNAs were differentially expressed in this integrative analysis. Following this, mRNA, miRNA and lncRNA regulatory or co?expression networks were constructed. From the construction of the regulatory networks, five miRNAs and ten lncRNAs were identified as key differentially expressed noncoding RNAs associated with HCC progression. Finally, the regulatory effects of ten lncRNAs and miRNAs were validated. The study provides a novel insight into the understanding of the transcriptional regulation of HCC, and differentially expressed lncRNAs targeted and regulated by miRNAs were identified and validated in HCC specimens and cell lines.

SUBMITTER: Xu JH

PROVIDER: S-EPMC5928629 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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The mRNA, miRNA and lncRNA networks in hepatocellular carcinoma: An integrative transcriptomic analysis from Gene Expression Omnibus.

Xu Jian-Hua JH Chang Wei-Hua WH Fu Hang-Wei HW Yuan Tao T Chen Ping P

Molecular medicine reports 20180307 5

Research advances and analysis in the non‑protein coding part of the human genome have suggested that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are associated with tumor initiation, growth and metastasis. Accumulating studies have demonstrated that a class of miRNAs and lncRNAs are dysregulated in hepatocellular carcinoma (HCC) and closely associated with tumorigenesis, diagnosis and prognosis. In the present study, integrative analysis of published data on multi‑level Gene Expression ...[more]

PMID: 29512731

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Project description:Background: Hepatocellular carcinoma (HCC) accounts for the majority of liver cancer, with the incidence and mortality rates increasing every year. Despite the improvement of clinical management, substantial challenges remain due to its high recurrence rates and short survival period. This study aimed to identify potential diagnostic and prognostic biomarkers in HCC through bioinformatic analysis. Methods: Datasets from GEO and TCGA databases were used for the bioinformatic analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out by WebGestalt website and clusterProfiler package of R. The STRING database and Cytoscape software were used to establish the protein-protein interaction (PPI) network. The GEPIA website was used to perform expression analyses of the genes. The miRDB, miRWalk, and TargetScan were employed to predict miRNAs and the expression levels of the predicted miRNAs were explored via OncomiR database. LncRNAs were predicted in the StarBase and LncBase while circRNA prediction was performed by the circBank. ROC curve analysis and Kaplan-Meier (KM) survival analysis were performed to evaluate the diagnostic and prognostic value of the gene expression, respectively. Results: A total of 327 upregulated and 422 downregulated overlapping DEGs were identified between HCC tissues and noncancerous liver tissues. The PPI network was constructed with 89 nodes and 178 edges and eight hub genes were selected to predict upstream miRNAs and ceRNAs. A lncRNA/circRNA-miRNA-mRNA network was successfully constructed based on the ceRNA hypothesis, including five lncRNAs (DLGAP1-AS1, GAS5, LINC00665, TYMSOS, and ZFAS1), six circRNAs (hsa_circ_0003209, hsa_circ_0008128, hsa_circ_0020396, hsa_circ_0030051, hsa_circ_0034049, and hsa_circ_0082333), eight miRNAs (hsa-miR-150-5p, hsa-miR-19b-3p, hsa-miR-23b-3p, hsa-miR-26a-5p, hsa-miR-651-5p, hsa-miR-10a-5p, hsa-miR-214-5p and hsa-miR-486-5p), and five mRNAs (CDC6, GINS1, MCM4, MCM6, and MCM7). The ceRNA network can promote HCC progression via cell cycle, DNA replication, and other pathways. Clinical diagnostic and survival analyses demonstrated that the ZFAS1/hsa-miR-150-5p/GINS1 ceRNA regulatory axis had a high diagnostic and prognostic value. Conclusion: These results revealed that cell cycle and DNA replication pathway could be potential pathways to participate in HCC development. The ceRNA network is expected to provide potential biomarkers and therapeutic targets for HCC management, especially the ZFAS1/hsa-miR-150-5p/GINS1 regulatory axis.

Project description:Liver hepatocellular carcinoma (LIHC) is one of the major causes of cancer-related death worldwide with increasing incidences, however there are very few studies about the underlying mechanisms and pathways in the development of LIHC. We obtained LIHC samples from The Cancer Genome Atlas (TCGA) to screen differentially expressed mRNAs, lncRNAs, miRNAs and driver mutations. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene ontology enrichment analyses and protein-protein interaction (PPI) network were performed. Moreover, we constructed a competing endogenous lncRNAs-miRNAs-mRNAs network. Finally, cox proportional hazards regression analysis was used to identify important prognostic differentially expressed genes. Total of 1284 mRNAs, 123 lncRNAs, 47 miRNAs were identified within different tissues of LIHC patients. GO analysis indicated that upregulated and downregulated differentially expressed mRNAs (DEmRNAs) were mainly associated with cell division, DNA replication, mitotic sister chromatid segregation and complement activation respectively. Meanwhile, KEGG terms revealed that upregulated and downregulated DEmRNAs were primarily involved in DNA replication, Metabolic pathways, cell cycle and Metabolic pathways, chemical carcinogenesis, retinol metabolism pathway respectively. Among the DERNAs, 542 lncRNAs-miRNAs-mRNAs pairs were predicted to construct a ceRNA regulatory network including 35 DElncRNAs, 26 DEmiRNAs and 112 DEmRNAs. In the Kaplan-Meier analysis, total of 43 mRNAs, 14 lncRNAs and 3 miRNAs were screened out to be significantly correlated with overall survival of LIHC. The mutation signatures were analyzed and its correlation with immune infiltrates were evaluated using the TIMER in LIHC. Among the mutation genes, TTN mutation is often associated with poor immune infiltration and a worse prognosis in LIHC. This work conducted a novel lncRNAs-miRNAs-mRNAs network and mutation signatures for finding potential molecular mechanisms underlying the development of LIHC. The biomarkers also can be used for predicting prognosis of LIHC.

Dataset Information

The mRNA, miRNA and lncRNA networks in hepatocellular carcinoma: An integrative transcriptomic analysis from Gene Expression Omnibus.

Publications

The mRNA, miRNA and lncRNA networks in hepatocellular carcinoma: An integrative transcriptomic analysis from Gene Expression Omnibus.

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