Origins of DNA methylation defects in Wilms tumors

Anvar, Zahra; Acurzio, Basilia; Roma, Josep; Cerrato, Flavia; Verde, Gaetano

doi:10.1016/j.canlet.2019.05.013

Cited by 27 publications

(23 citation statements)

References 120 publications

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“…Wilms' tumor (WT), also known as nephroblastoma, is an embryonal childhood tumor that accounts for 90% of childhood renal tumors and 7% of all childhood cancers [1]. Due to the successive clinical trials conducted by several collaborative clinical trial groups around the world, such as the International Society of Paediatric Oncology (SIOP), and the National Wilms' Tumor Study Group (NWTSG), treatment regimen that the combination of nephrectomy and chemotherapy was found to greatly improve overall survival (OS) rates exceeding 90% [2]. Overall, WT treatment can be considered as a successful story.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of lncRNA‐Mediated ceRNA Crosstalk and Identification of Prognostic Biomarkers in Wilms’ Tumor

Zheng

Liu

et al. 2020

BioMed Research International

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Wilms’ tumor (WT) is the most common type of childhood kidney cancer, and most cases present with favorable histology and respond well to standard treatment. However, a subset of patients with WT is diagnosed with bilateral, relapsed, and high-risk tumors which remain the leading cause of cancer-related death in children. Long noncoding RNAs (lncRNAs) and their aberrant expression have currently been attracting great attention as oncogenes or tumor suppressors during tumor initiation and progression. So far, their roles and related competitive endogenous RNA (ceRNA) network remain unelucidated in nephroblastoma pathogenesis. We comprehensively integrated lncRNA, microRNA (miRNA), and messenger RNA (mRNA) expression profiles from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and screened out differentially expressed mRNAs (DEMs), lncRNAs (DELs), and miRNAs (DEMis) to construct a ceRNA network based on the information generated from miRcode, miRTarBase, TargetScan, and miRDB. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to analyze the functional characteristics of DEMs in the ceRNA network. The interaction between protein molecules was also analyzed by establishing a protein-protein interaction network. Finally, prognosis-related biomarkers were identified via survival analysis. Initially, 1647 DELs, 115 DEMis, and 3280 DEMs (|log FC| > 2; FDR < 0.01) were obtained using the R package. Next, we constructed a lncRNA-miRNA-mRNA network (ceRNA network), in which 176 DELs, 24 DEMis, and 141 DEMs were identified. Furthermore, 148 functional enrichment terms from GO were identified and 29 KEGG pathways were found to be significantly enriched. We also integrated patient clinical information to analyze the association between DERNAs and patient prognosis. We found that high expression of 8 DELs (LINC00473, AL445228.2, DENND5B−AS1, DLEU2, AC123595.1, AC135178.1, LINC00535, and LMO7−AS1) and 4 DEMs (CEP55, DEPDC1, PHF19, and TRIM36) correlated with poor survival in a patient with WT, whereas high expression of 2 DELs (MEG3 and RMST), 1 DEM (KIAA0922), and 1 DEMi (hsa−mir−200a) could possibly lead to better clinical outcomes. For the first time, the present study provided a novel insight into lncRNA-related ceRNA networks and identified potential prognostic biomarkers in Wilms’ tumor.

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Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of lncRNA‐Mediated ceRNA Crosstalk and Identification of Prognostic Biomarkers in Wilms’ Tumor

Zheng

Liu

et al. 2020

BioMed Research International

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“…Fortunately, with the development of treatments, the survival rate of children with WT has increased by nearly 60% (3). The International Society of Pediatric Oncology stated that the combination of nephrectomy and chemotherapy significantly improved overall survival (OS) by more than 90% (4). However, 25% of children still have a poor prognosis based on the tumor stage (5).…”

Section: Introductionmentioning

confidence: 99%

A Survival-Related Competitive Endogenous RNA Network of Prognostic lncRNAs, miRNAs, and mRNAs in Wilms Tumor

et al. 2021

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Wilms tumor (WT) commonly occurs in infants and children. We evaluated clinical factors and the expression of multiple RNAs in WT samples in the TARGET database. Eight long non-coding RNAs (lncRNAs; AC079310.1, MYCNOS, LINC00271, AL445228.3, Z84485.1, AC091180.5, AP002518.2, and AC007879.3), two microRNAs (miRNAs; hsa-mir-152 andhsa-mir-181a), and nine messenger RNAs (mRNAs; TCTEX1D4, RNF133, VRK1, CCNE1, HEY1, C10orf71, SPRY1, SPAG11A, and MAGEB18) were screened from differentially expressed RNAs and used to construct predictive survival models. These models showed good prognostic ability and were highly correlated with tumor stage and histological classification. Additionally, survival-related ceRNA network was constructed using 35 RNAs (15 lncRNAs, eight miRNAs, and 12 mRNAs). KEGG pathway analysis suggested the “Wnt signaling pathway” and “Cellular senescence” as the main pathways. In conclusion, we established a multinomial predictive survival model and a survival-related ceRNA network, which provide new potential biomarkers that may improve the prognosis and treatment of WT patients.

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“…Nephroblastoma has a complex etiology that is poorly understood. Although the molecular mechanisms of nephroblastoma remain undiscovered, increasing evidence suggests that genetic and epigenetic characteristics play an important role in the disease process [1].…”

Section: Introductionmentioning

confidence: 99%

Genome-wide screening of m6A-modified transcript in the Wilms’ tumor

Liu

et al. 2021

Preprint

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Background Wilms’ tumor, also called nephroblastoma, is the most common pediatric renal malignancy. The pathogenesis of Wilms’ tumor has been attributed to several genetic and epigenetic factors. However, the most pervasive internal mRNA modification that affects almost every process of RNA metabolism, RNA N6-Methyladenosine (m6A) methylation, has not been characterized in Wilms’ tumor. Methods Wilms’ tumor (WT) and adjacent non-cancerous (NC) tissue samples were obtained from 23 children with nephroblastoma, and the global m6A levels were measured by mass spectrometry. Analyses by m6A-mRNA epitranscriptomic microarray and mRNA microarray were performed, and m6A-related mRNAs were validated by quantitative real-time PCR for input and m6A-immunoprecipitated RNA samples from WT and NC tissues. Gene ontology analysis and KEGG pathway analysis were performed for differentially expressed genes, and expression of RNA methylation-related factors was measured by quantitative real-time PCR. Results The total m6A methylation levels in total RNA of WT samples and NC samples were (0.21 ± 0.01)% and (0.22 ± 0.01)%, respectively, with no statistically significant difference. Fifty-nine transcripts were differentially m6A-methylated between the WT and NC groups, which showed distinct m6A modification patterns. Gene ontology analysis indicated that m6A-modified genes were enriched in cancer-associated pathways, including the mTOR pathway, and conjoint analysis of the unique methylation and gene expression patterns in WT samples suggested an association with metabolic pathways.The mRNA levels of the m6A-related “reader” genes, YTHDF1, YTHDF2 and IGF2BP3, were statistically higher in WT samples than in NC samples. Conclusion This is the first study to determine the m6A modification profiles in Wilms’ tumor. Our data provide novel information regarding patterns of m6A modification that correlate with carcinogenesis in Wilms’ tumor.

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Origins of DNA methylation defects in Wilms tumors

Cited by 27 publications

References 120 publications

Comprehensive Analysis of lncRNA‐Mediated ceRNA Crosstalk and Identification of Prognostic Biomarkers in Wilms’ Tumor

Comprehensive Analysis of lncRNA‐Mediated ceRNA Crosstalk and Identification of Prognostic Biomarkers in Wilms’ Tumor

A Survival-Related Competitive Endogenous RNA Network of Prognostic lncRNAs, miRNAs, and mRNAs in Wilms Tumor

Genome-wide screening of m6A-modified transcript in the Wilms’ tumor

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