Dataset Information

Prediction of circRNAs Based on the DNA Methylation-Mediated Feature Sponge Function in Breast Cancer.

ABSTRACT: Several studies have found that DNA methylation is associated with transcriptional regulation and affect sponge regulation of non-coding RNAs in cancer. The integration of circRNA, miRNA, DNA methylation and gene expression data to identify sponge circRNAs is important for revealing the role of DNA methylation-mediated regulation of sponge circRNAs in cancer progression. We established a DNA methylation-mediated circRNA crosstalk network by integrating gene expression, DNA methylation and non-coding RNA data of breast cancer in TCGA. Four modules (26 candidate circRNAs) were mined. Next, 10 DNA methylation-mediated sponge circRNAs (sp_circRNAs) and five sponge driver genes (sp_driver genes) in breast cancer were identified in the CMD network using a computational process. Among the identified genes, ERBB2 was associated with six sponge circRNAs, which illustrates its better sponge regulatory function. Survival analysis showed that DNA methylations of 10 sponge circRNA host genes are potential prognostic biomarkers in the TCGA dataset (p = 0.0239) and GSE78754 dataset (p = 0.0377). In addition, the DNA methylation of two sponge circRNA host genes showed a significant negative correlation with their driver gene expressions. We developed a strategy to predict sponge circRNAs by DNA methylation mediated with playing the role of regulating breast cancer sponge driver genes.

SUBMITTER: Gu Y

PROVIDER: S-EPMC6988805 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Prediction of circRNAs Based on the DNA Methylation-Mediated Feature Sponge Function in Breast Cancer.

Gu Yue Y Ci Ce C Zhang Xingda X Su Mu M Lv Wenhua W Chen Chuangeng C Liu Hui H Zhang Dongwei D Zhang Shumei S Zhang Yan Y

Frontiers in bioengineering and biotechnology 20191126

Several studies have found that DNA methylation is associated with transcriptional regulation and affect sponge regulation of non-coding RNAs in cancer. The integration of circRNA, miRNA, DNA methylation and gene expression data to identify sponge circRNAs is important for revealing the role of DNA methylation-mediated regulation of sponge circRNAs in cancer progression. We established a DNA methylation-mediated circRNA crosstalk network by integrating gene expression, DNA methylation and non-co ...[more]

PMID: 32039169

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Project description:We present a method that utilizes DNA methylation profiling for prediction of the cytogenetic subtypes of acute lymphoblastic leukemia (ALL) cells from pediatric ALL patients. The primary aim of our study was to improve risk stratification of ALL patients into treatment groups using DNA methylation as a complement to current diagnostic methods. A secondary aim was to gain insight into the functional role of DNA methylation in ALL.We used the methylation status of ~450,000 CpG sites in 546 well-characterized patients with T-ALL or seven recurrent B-cell precursor ALL subtypes to design and validate sensitive and accurate DNA methylation classifiers. After repeated cross-validation, a final classifier was derived that consisted of only 246 CpG sites. The mean sensitivity and specificity of the classifier across the known subtypes was 0.90 and 0.99, respectively. We then used DNA methylation classification to screen for subtype membership of 210 patients with undefined karyotype (normal or no result) or non-recurrent cytogenetic aberrations ('other' subtype). Nearly half (n?=?106) of the patients lacking cytogenetic subgrouping displayed highly similar methylation profiles as the patients in the known recurrent groups. We verified the subtype of 20% of the newly classified patients by examination of diagnostic karyotypes, array-based copy number analysis, and detection of fusion genes by quantitative polymerase chain reaction (PCR) and RNA-sequencing (RNA-seq). Using RNA-seq data from ALL patients where cytogenetic subtype and DNA methylation classification did not agree, we discovered several novel fusion genes involving ETV6, RUNX1, and PAX5.Our findings indicate that DNA methylation profiling contributes to the clarification of the heterogeneity in cytogenetically undefined ALL patient groups and could be implemented as a complementary method for diagnosis of ALL. The results of our study provide clues to the origin and development of leukemic transformation. The methylation status of the CpG sites constituting the classifiers also highlight relevant biological characteristics in otherwise unclassified ALL patients.

Dataset Information

Prediction of circRNAs Based on the DNA Methylation-Mediated Feature Sponge Function in Breast Cancer.

Publications

Prediction of circRNAs Based on the DNA Methylation-Mediated Feature Sponge Function in Breast Cancer.

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