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Integrated Analysis of the lncRNA-Associated ceRNA Network in Wilms Tumor via TARGET and GEO Databases
Biao An1, Yuan Hu1, Xiao Liang1
1Department of Gynecology and Obstetrics, Development and Related Disease of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, China.
Abstract:
Wilms tumor (WT) is the most common genitourinary renal tumor that typically occurs in children under 15 and is thought to be linked to somatic and germline mutations. However, the specific functional role of competing endogenous RNAs (ceRNAs) and their potential implications in WT remain unclear. In this study, we developed an lncRNA-mediated (long noncoding RNA-mediated) ceRNA network via the R packages for WT with expression data obtained from the tumor alterations relevant for genomics-driven therapy (TARGET) database. Unsupervised hierarchical clustering analysis revealed that the WT specimens could be clearly distinguished from healthy specimens with respect to the expression of disordered RNAs. A total of 1,607 differentially expressed (DE) lncRNAs, 116 DE microRNAs (DEmiRNAs), and 3,262 DE messenger RNAs (DEmRNAs) were identified as WT-specific RNAs, and a lncRNA-miRNA-mRNA ceRNA network with 159 DElncRNAs, 18 DEmiRNAs, 131 DEmRNAs, and 792 interactions was constructed. According to the clinical survival data, 12 DElncRNAs, 5 DEmRNAs, and 2 DEmiRNAs were selected from the ceRNA network that could significantly impact the overall survival of WT patients (P < 0.05). Functional enrichment analysis showed that the biological processes and pathways of DEmRNAs, such as cell cycle and virus infection, may be associated with WT. The present study constructed a dysregulated lncRNA-mediated ceRNA network in WT and discovered that lncRNA-mediated ceRNAs may serve as important regulators in WT development and progression. Survival-associated RNAs may serve as new potential biomarkers, suggesting that the constructed ceRNA network in WT might be important for determining optimal therapeutic strategies.
Insights
This study reveals a network of long noncoding RNAs (lncRNAs) involved in Wilms tumor (WT) development. These RNA interactions may offer new biomarkers and therapeutic targets for pediatric kidney cancer.
Area of Science:
- Oncology
- Genetics
- Bioinformatics
Background:
- Wilms tumor (WT) is a common pediatric kidney cancer, often linked to genetic mutations.
- The role of competing endogenous RNAs (ceRNAs) in WT pathogenesis is not well understood.
Purpose of the Study:
- To construct and analyze a lncRNA-mediated ceRNA network in Wilms tumor.
- To identify potential RNA biomarkers and therapeutic targets for WT.
Main Methods:
- Utilized R packages and expression data from the TARGET database to build the ceRNA network.
- Applied unsupervised hierarchical clustering to distinguish WT from healthy specimens.
- Identified differentially expressed long noncoding RNAs (DElncRNAs), microRNAs (DEmiRNAs), and messenger RNAs (DEmRNAs).
Main Results:
- A WT-specific ceRNA network comprising 159 DElncRNAs, 18 DEmiRNAs, and 131 DEmRNAs with 792 interactions was constructed.
- 1,607 DElncRNAs, 116 DEmiRNAs, and 3,262 DEmRNAs were identified.
- 12 DElncRNAs, 5 DEmRNAs, and 2 DEmiRNAs were found to significantly impact patient survival (P < 0.05).
Conclusions:
- The study established a dysregulated lncRNA-mediated ceRNA network in WT.
- lncRNA-mediated ceRNAs are likely key regulators in WT development and progression.
- Survival-associated RNAs identified may serve as novel biomarkers for therapeutic strategies in WT.
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