WT is a type of paediatric renal malignancy. Although overall survival in WT patients is constantly improved, disease recurrence and poor prognosis are still the main causes of cancer-related death in childhood . Dysregulated genes are considered to be the major cause of tumorigenesis in WT. Recently, increasing attention has been paid to the crucial roles of the ceRNA network in gene expression regulation at the transcription, post-transcription and translation levels). A previous study reported the regulatory role of ceRNA networks in the proliferation, metastasis and invasion of cancer [14, 15]. To better understand how the ceRNA regulatory network affects WT, large-scale WT data from the TARGET database were analysed, and a dysregulated ceRNA regulatory network in WT was successfully constructed. A dysregulated ceRNA network in WT was constructed according to the interactions of 980 DEL–DEM pairs and 235 DEM–DEG pairs between 205 DELs, 26 DEMs, and 143 DEGs. In addition, Kaplan-Meier curves were generated to identify prognostic biomarkers in WT. Fourteen differentially expressed lncRNAs (AC005609.1, AC135178.1, ADAMTS9-AS1, AL391832.1, AL445228.2, DENND5B-AS1, DLEU2, GRM7-AS3, LINC00303, LINC00473, MEG3, MYB-AS1, NRG1-IT1, and RMST), 1 differentially expressed miRNA (hsa-mir-200a) and 8 differentially expressed mRNAs (CDCA4, CEP55, DEPDC1, KIAA0922, OSR1, PHF19, PLEKHA8, and ZBTB4) were shown to be significantly associated with the overall survival rate in WT.
Long noncoding RNAs (lncRNAs) are defined as noncoding RNAs longer than 200 nucleotides . lncRNAs were shown to be involved in a variety of biological regulatory functions, including metastasis and tumorigenesis of cancer [17, 18]. A total of 1,247 upregulated and 790 downregulated DELs were identified in the present study. A total of 205 DELs were included in the construction of the ceRNA network. Additionally, 14 out of the 205 DELs were associated with overall survival in WT patients (P < 0.05). Some differentially expressed lncRNAs in our analysis have been investigated in WT: for example, LINC00473 was show to be capable of decreasing miR-195 expression levels and inhibiting miR-195 function in WT . A dysregulated lncRNA signature including LINC00473/miR-195/IKKα was shown to play a protumorigenic pathogenesis role in WT . The abovementioned molecular experiments partially supported our results in the present study. The identified lncRNAs might serve as prognostic biomarkers and therapeutic targets in WT. In previous studies, RMST was shown to possibly inhibit cell proliferation, invasion, and migration, enhance cell apoptosis, and regulate the cell cycle to act as a tumour suppressor in triple-negative breast cancer . MEG3, a myeloid-related lncRNA, plays a tumour suppressor role in various solid neoplasms [20, 21]. DLEU2 was shown to control miR-16-1 to regulate proliferation, invasion and migration in laryngeal cancer . ADAMTS9-AS1 was related to the overall survival of breast cancer , bladder cancer  and colon adenocarcinoma  patients. Few studies, however, have explored the relationship between the abovementioned DELs and tumorigenesis in WT. Additionally, little is known about the regulatory role of LINC00303, GRM7-AS3, DLEU2, DENND5B-AS1, AL445228.2, AL391832.1, AC135178.1 and AC005609.1 in cancer. Therefore, further studies are needed to illuminate the molecular and biological mechanisms of these DELs in WT.
MicroRNAs are single-stranded and 18-25 nucleotide-long noncoding RNAs that target mRNAs to control gene expression . DEMs in WT, including 105 upregulated and 49 downregulated DEMs, were summarized in the present study. In the present study, the ceRNA network contained 14 differentially expressed miRNAs. However, only one miRNA (miR-200a) was related to overall survival in WT patients. miR-200a is an important member of the miR-200 family. It has been reported that miR-200a participates in several biological processes to control the progression of cancer [27, 28]. miR-200a was shown to target FOXA1 and act as a tumour suppressor in the survival, proliferation and invasion of glioma cells . In addition, miR-200a might inactivate BRD4-mediated AR signalling to inhibit the progression of prostate cancer . Moreover, previous studies have reported that miR-200a participates in the development and occurrence of oesophageal cancer, breast cancer and endometrial cancer by targeting specific genes, such as CRMP‐1, EPHA2 and PTEN [29-31]. However, there is no research to clearly elucidate the role of miR-200a in WT. The understanding of the role of miR-200a in the progression of WT is limited and requires more targeted molecular studies.
To further investigate the related cellular mechanisms in WT, GO and KEGG analyses of 143 DEGs in the ceRNA network were performed. The GO analysis results showed that the DEGs were mainly enriched in terms related to response to mechanical stimuli, transcription factor complexes and transcription factor activity (related to RNA polymerase II proximal promoter sequence-specific DNA binding). The KEGG analysis results indicated that DEGs in the ceRNA network were mainly enriched in pathways related to the cell cycle, small-cell lung cancer, p53 signalling, microRNAs in cancer, and cellular senescence. In recent years, many studies have reported the same findings. The PI3K-AKT-p53 signalling pathway is involved in the tumorigenesis of WT and might represent a potential target in the future . MiRNAs, which are single-stranded and 18-25-nucleotide-long noncoding RNAs , were involved in regulating proliferation, the cell cycle and apoptosis in WT [33, 34]. Cellular senescence was reported to be responsible for restricted proliferation in WT, and this result was linked to increased p21 expression and was independent of p53 expression . The abovementioned related studies and experiments partially support our GO and KEGG analysis results in the present study.
The major limitation of the present study is that confirmation of the differentially expressed lncRNAs, miRNAs, mRNA and relative pathways in tumour tissues and blood is lacking. Further targeted studies related to this ceRNA network need to be designed to verify and investigate these valuable ncRNAs in the progression of WT.