Integrated Analysis of the lncRNA-Associated ceRNA Network in Wilms Tumor via TARGET and GEO Databases.

IF 1.4 4区 生物学 Q4 GENETICS & HEREDITY
Biao An, Yuan Hu, Xiao Liang
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引用次数: 0

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.

基于TARGET和GEO数据库对Wilms肿瘤中lncrna相关ceRNA网络的综合分析
肾母细胞瘤(WT)是最常见的泌尿生殖系统肿瘤,通常发生在15岁以下的儿童中,被认为与体细胞和种系突变有关。然而,竞争内源性rna (ceRNAs)的具体功能作用及其在WT中的潜在意义尚不清楚。在这项研究中,我们通过WT的R包开发了一个lncrna介导的(长链非编码rna介导的)ceRNA网络,该网络的表达数据来自与基因组学驱动治疗(TARGET)数据库相关的肿瘤改变。无监督的分层聚类分析表明,就无序rna的表达而言,WT标本可以与健康标本明显区分开。共鉴定出1607个差异表达(DE) lncrna、116个DE microrna (demirna)和3262个DE信使rna (demrna)为wt特异性rna,构建了包含159个delncrna、18个demirna、131个demrna和792个相互作用的lncRNA-miRNA-mRNA ceRNA网络。根据临床生存数据,从ceRNA网络中筛选出12个能够显著影响WT患者总体生存的delncrna、5个demmrna和2个demirna (P < 0.05)。功能富集分析表明,细胞周期、病毒感染等demrna的生物学过程和途径可能与WT有关。本研究构建了WT中lncrna介导的失调ceRNA网络,发现lncrna介导的ceRNA可能在WT的发育和进展中发挥重要调节作用。存活相关rna可能作为新的潜在生物标志物,这表明在WT中构建的ceRNA网络可能对确定最佳治疗策略很重要。
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来源期刊
Genetics research
Genetics research 生物-遗传学
自引率
6.70%
发文量
74
审稿时长
>12 weeks
期刊介绍: Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.
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