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Published on: March 30, 2019
Comprehensive analysis of long non‑coding RNA using an associated competitive endogenous RNA network in Wilms tumor
Zhichao Wang1, Huiyan Cheng2, Lingli Qi3
1Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
Abstract:
Wilms tumor (WT) is the most common malignant renal neoplasm in children; however, the underlying molecular mechanisms are not well understood. According to the competing endogenous RNA (ceRNA) theory, long non‑coding RNAs (lncRNAs) can regulate the expression of target genes by adsorbing microRNAs (miRNAs/miRs). However, the role of lncRNAs in WT has not been fully elucidated. The aim of the present study was to construct a ceRNA network to identify the potential lncRNAs involved in WT. The expression profiles of lncRNAs, miRNAs and mRNAs in 120 WT and six normal tissues were obtained from the Therapeutically Applicable Research to Generate Effective Treatments database. A total of 442 lncRNAs, 214 miRNAs and 4,912 mRNAs were identified as differentially expressed in WT and were enriched in 472 Gene Ontology terms (355 biological processes, 89 cellular components and 29 molecular functions) and 18 Kyoto Encyclopedia of Genes and Genomes pathways. A lncRNA‑miRNA‑mRNA ceRNA network of WT consisting of with 32 lncRNAs, 14 miRNAs and 158 mRNAs was constructed, based on the bioinformatics analysis of the miR target prediction database and the miRNAcode, miRTarBase and TargetScan databases. Subsequently, three lncRNAs, three miRNAs and 17 mRNAs, which had a significant effect on the overall survival rate of patients with WT, were identified based on the survival analysis. The three lncRNAs were also differentially expressed in the late and early stages of WT and were validated using the GSE66405 dataset obtained from the Gene Expression Omnibus database. In conclusion, the present study generated a specific lncRNA‑related ceRNA network of WT, which may provide a novel perspective on the molecular mechanisms underlying the progression and prognosis of the disease.
Insights
This study identifies key long non-coding RNAs (lncRNAs) involved in Wilms tumor (WT) by constructing a competing endogenous RNA (ceRNA) network. These findings offer new insights into WT progression and patient prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Wilms tumor (WT) is a common pediatric kidney cancer with poorly understood molecular drivers.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their regulatory roles in cancer via the competing endogenous RNA (ceRNA) mechanism.
- The specific involvement of lncRNAs in WT pathogenesis remains largely unelucidated.
Purpose of the Study:
- To construct a comprehensive lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network for Wilms tumor (WT).
- To identify potential lncRNAs that play a significant role in WT development and patient survival.
- To provide a novel perspective on the molecular mechanisms underlying WT progression and prognosis.
Main Methods:
- Utilized expression profile data for lncRNAs, miRNAs, and mRNAs from the Therapeutically Applicable Research to Generate Effective Treatments (TREAT) database for 120 WT and 6 normal tissues.
- Performed bioinformatics analyses, including differential expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and ceRNA network construction using miR target prediction databases.
- Conducted survival analysis to identify key molecular players and validated findings using the Gene Expression Omnibus (GEO) dataset GSE66405.
Main Results:
- Identified 442 differentially expressed lncRNAs, 214 miRNAs, and 4,912 mRNAs in WT tissues.
- Constructed a WT-specific ceRNA network comprising 32 lncRNAs, 14 miRNAs, and 158 mRNAs.
- Discovered three lncRNAs, three miRNAs, and 17 mRNAs significantly associated with overall patient survival, with three lncRNAs showing differential expression in early and late WT stages.
Conclusions:
- A novel lncRNA-related ceRNA network specific to Wilms tumor has been successfully generated.
- The identified lncRNAs may serve as potential biomarkers for WT prognosis and therapeutic targets.
- This study enhances our understanding of the molecular landscape of Wilms tumor, paving the way for future research.
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