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Integrated analysis of differentially expressed profiles and construction of a competing endogenous long non-coding RNA network in renal cell carcinoma.

ABSTRACT: Background:Long non-coding RNAs (lncRNAs) play crucial roles in the initiation and progression of renal cell carcinoma (RCC) by competing in binding to miRNAs, and related competitive endogenous RNA (ceRNA) networks have been constructed in several cancers. However, the coexpression network has been poorly explored in RCC. Methods:We collected RCC RNA expression profile data and relevant clinical features from The Cancer Genome Atlas (TCGA). A cluster analysis was explored to show different lncRNA expression patterns. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and gene set enrichment analysis (GSEA) were performed to analyze the functions of the intersecting mRNAs. Targetscan and miRanda bioinformatics algorithms were used to predict potential relationships among RNAs. Univariate Cox proportional hazards regression was conducted to determine the RNA expression levels and survival times. Results:Bioinformatics analysis revealed that the expression profiles of hundreds of aberrantly expressed lncRNAs, miRNAs, and mRNAs were significantly changed between different stages of tumors and non-tumor groups. By combining the data predicted by databases with intersection RNAs, a ceRNA network consisting of 106 lncRNAs, 26 miRNAs and 69 mRNAs was established. Additionally, a protein interaction network revealed the main hub nodes (VEGFA, NTRK2, DLG2, E2F2, MYB and RUNX1). Furthermore, 63 lncRNAs, four miRNAs and 31 mRNAs were significantly associated with overall survival. Conclusion:Our results identified cancer-specific lncRNAs and constructed a ceRNA network for RCC. A survival analysis related to the RNAs revealed candidate biomarkers for further study in RCC.

SUBMITTER: Xing Q

PROVIDER: S-EPMC6054097 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Integrated analysis of differentially expressed profiles and construction of a competing endogenous long non-coding RNA network in renal cell carcinoma.

Xing Qianwei Q Huang Yeqing Y Wu You Y Ma Limin L Cai Bo B

PeerJ 20180717

<h4>Background</h4>Long non-coding RNAs (lncRNAs) play crucial roles in the initiation and progression of renal cell carcinoma (RCC) by competing in binding to miRNAs, and related competitive endogenous RNA (ceRNA) networks have been constructed in several cancers. However, the coexpression network has been poorly explored in RCC.<h4>Methods</h4>We collected RCC RNA expression profile data and relevant clinical features from The Cancer Genome Atlas (TCGA). A cluster analysis was explored to show ...[more]

PMID: 30038853

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Project description:BackgroundHuntington's disease (HD) is one of the most common polyglutamine disorders, leading to progressive dyskinesia, cognitive impairment, and neuropsychological problems. Besides the dysregulation of many protein-coding genes in HD, previous studies have revealed a variety of non-coding RNAs that are also dysregulated in HD, including several long non-coding RNAs (lncRNAs). However, an integrated analysis of differentially expressed (DE) genes based on a competing endogenous RNA (ceRNA) network is still currently lacking.MethodsIn this study, we have systematically analyzed the gene expression profile data of neural progenitor cells (NPCs) derived from patients with HD and controls (healthy controls and the isogenic controls of HD patient cell lines corrected using a CRISPR-Cas9 approach at the HTT locus) to screen out DE mRNAs and DE lncRNAs and create a ceRNA network. To learn more about the possible functions of lncRNAs in the ceRNA regulatory network in HD, we conducted a functional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and established a protein-protein interaction (PPI) network for mRNAs interacting with these lncRNAs.ResultsWe identified 490 DE mRNAs and 94 DE lncRNAs, respectively. Of these, 189 mRNAs and 20 lncRNAs were applied to create a ceRNA network. The results showed that the function of DE lncRNAs mainly correlated with transcriptional regulation as demonstrated by GO analysis. Also, KEGG enrichment analysis showed these lncRNAs were involved in tumor necrosis factor, calcium, Wnt, and NF-kappa B signaling pathways. Interestingly, the PPI network revealed that a variety of transcription factors in the ceRNA network interacted with each other, suggesting such lncRNAs may regulate transcription in HD by controlling the expression of such protein-coding genes, especially transcription factors.ConclusionsOur research provides new clues for uncovering the mechanisms of lncRNAs in HD and can be used as the focus for further investigation.

Project description:The competing endogenous RNA (ceRNA) network is crucial for the development and progression of tumors, including non‑small cell lung cancer (NSCLC). However, what type of ceRNA network regulates NSCLC has not been clarified. The present study aimed to elucidate the long non‑coding RNA (lncRNA)/microRNA (miRNA)/mRNA ceRNA network in NSCLC, particularly for the significance of lncRNAs in NSCLC. NSCLC‑specific differentially expressed lncRNAs, miRNAs and mRNAs in the Cancer Genome Atlas (TCGA) were analyzed and their relationship was analyzed by a ceRNA network. Their potential functions of differentially expressed mRNAs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, the expression levels of four selected lncRNAs in TCGA were determined and their associated survival of patients was examined. In addition, the expression profiles of these four lncRNAs in 48 NSCLC specimens and cell lines, their cellular distribution and associated clinical parameters were examined. We successfully constructed a ceRNA network, including 113 lncRNAs, 12 miRNAs and 36 mRNAs differentially expressed between NSCLC and non‑tumor tissues. LINC00525, MED4‑AS1, STEAP2‑AS1 and SYNPR‑AS1 lncRNAs were selected and validated for their association with the survival of NSCLC patients. The expression of these lncRNAs was upregulated in 48 NSCLC tissues and was varying in NSCLC cells. While LINC00525 was mainly expressed in the cytoplasm, MED4‑AS1 was in both the nucleus and cytoplasm of A549 cells. In addition, the expression of LINC00525 was significantly associated with smoking history (P<0.05); MED4‑AS1 was significantly associated with women, poor differentiation and lymph node metastasis (P<0.05); STEAP2‑AS1 was significantly associated with women (P<0.01); and SYNPR‑AS1 was significantly associated with women and adenocarcinoma (P<0.05). These lncRNAs may be valuable biomarkers for prognosis of NSCLC and the ceRNA network may provide new insights in the pathogenesis of NSCLC.

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Dataset Information

Integrated analysis of differentially expressed profiles and construction of a competing endogenous long non-coding RNA network in renal cell carcinoma.

Publications

Integrated analysis of differentially expressed profiles and construction of a competing endogenous long non-coding RNA network in renal cell carcinoma.

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