Dataset Information

Functional Long Noncoding RNAs (lncRNAs) in Clear Cell Kidney Carcinoma Revealed by Reconstruction and Comprehensive Analysis of the lncRNA-miRNA-mRNA Regulatory Network.

ABSTRACT: BACKGROUND A variety of treatment strategies have been developed for clear cell kidney carcinoma (KIRC); however, there is still a need for effective therapeutic targets and prognostic molecular biomarkers. Given that long noncoding RNAs (lncRNAs) has been emerging as an important regulator in tumorigenesis, we explored potential functional lncRNAs in KIRC by comprehensively analyzing the lncRNA-miRNA-mRNA regulatory network with bioinformatics processing tools. MATERIAL AND METHODS RNA-seq/miRNA-seq data of KIRC in The Cancer Genome Atlas (TCGA) were obtained and analyzed. The "edgeR" package in R software was used to identify differentially expressed lncRNAs (DElncRNAs, differentially expressed long noncoding RNAs), miRNAs (DEmiRNAs, differentially expressed micro RNAs), and mRNAs (DEmRNAs, differentially expressed messenger RNAs) in KIRC and normal samples. A global triple network was conducted based on the competing endogenous RNA (ceRNA) theory, and survival analysis was conducted by "survival" package in R software. RESULTS A total of 4246 DElncRNAs, 179 DEmiRNAs, and 5758 DEmRNAs were identified, among which a subset of them (321 lncRNAs, 26 miRNAs, and 1068 mRNAs) were found to constitute a global ceRNA network in KIRC. Four lncRNAs (ENTPD3-AS1, FGD5-AS1, LIFR-AS1, and UBAC2-AS1) were revealed to be potential therapeutic targets as well as prognostic biomarkers of KIRC by our extensive functional analysis. CONCLUSIONS We reported here the identification of functional lncRNAs in KIRC via a TCGA data-based bioinformatics analysis. We believe that this study might contribute to improving the comprehension of the lncRNA-mediated ceRNA regulatory mechanisms in the tumorigenesis of KIRC. Meanwhile, our results suggested that 4 lncRNAs might act as potential therapeutic targets or candidate prognostic biomarkers in KIRC.

SUBMITTER: Zhu H

PROVIDER: S-EPMC6251074 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Functional Long Noncoding RNAs (lncRNAs) in Clear Cell Kidney Carcinoma Revealed by Reconstruction and Comprehensive Analysis of the lncRNA-miRNA-mRNA Regulatory Network.

Zhu Hehuan H Lu Jun J Zhao Hu H Chen Zhan Z Cui Qiang Q Lin Zhiwen Z Wang Xuyang X Wang Jie J Dong Huiyue H Wang Shuiliang S Tan Jianming J

Medical science monitor : international medical journal of experimental and clinical research 20181116

BACKGROUND A variety of treatment strategies have been developed for clear cell kidney carcinoma (KIRC); however, there is still a need for effective therapeutic targets and prognostic molecular biomarkers. Given that long noncoding RNAs (lncRNAs) has been emerging as an important regulator in tumorigenesis, we explored potential functional lncRNAs in KIRC by comprehensively analyzing the lncRNA-miRNA-mRNA regulatory network with bioinformatics processing tools. MATERIAL AND METHODS RNA-seq/miRN ...[more]

PMID: 30444862

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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.

Dataset Information

Functional Long Noncoding RNAs (lncRNAs) in Clear Cell Kidney Carcinoma Revealed by Reconstruction and Comprehensive Analysis of the lncRNA-miRNA-mRNA Regulatory Network.

Publications

Functional Long Noncoding RNAs (lncRNAs) in Clear Cell Kidney Carcinoma Revealed by Reconstruction and Comprehensive Analysis of the lncRNA-miRNA-mRNA Regulatory Network.

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