Key result
Epirubicin exposure in human cardiac microtissues significantly altered DNA methylation profiles, identifying 35 candidate genes with strong methylation alterations implicated in cardiac dysfunction.
Why the study?
Epirubicin is known for cardiotoxic side effects, and studying epigenetic modifications like DNA methylation can help clarify the underlying toxic mechanisms in cardiac tissue.
Does epirubicin alter DNA methylation and gene expression in human cardiac microtissues?
Does epirubicin alter DNA methylation and gene expression in human cardiac microtissues?
Epirubicin induces dose-dependent DNA methylation alterations in human cardiac microtissues, which correlate with changes in gene expression and may underlie its cardiotoxic effects.
Identifies candidate methylated genes in epirubicin cardiotoxicity model; hypothesis-generating and requires validation before clinical consideration.
BACKGROUND: Epirubicin (EPI) is an important anticancer drug that is well-known for its cardiotoxic side effect. Studying epigenetic modification such as DNA methylation can help to understand the EPI-related toxic mechanisms in cardiac tissue. In this study, we analyzed the DNA methylation profile in a relevant human cell model and inspected the expression of differentially methylated genes at the transcriptome level to understand how changes in DNA methylation could affect gene expression in relation to EPI-induced cardiotoxicity. METHODS: Human cardiac microtissues were exposed to either therapeutic or toxic (IC20) EPI doses during 2 weeks. The DNA and RNA were collected from microtissues in triplicates at 2, 8, 24, 72, 168, 240, and 336 hours of exposure. Methylated DNA immunoprecipitation-sequencing (MeDIP-seq) analysis was used to detect DNA methylation levels in EPI-treated and control samples. The MeDIP-seq data were analyzed and processed using the QSEA package with a recently published workflow. RNA sequencing (RNA-seq) was used to measure global gene expression in the same samples. RESULTS: After processing the MeDIP-seq data, we detected 35, 37, 15 candidate genes which show strong methylated alterations between all EPI-treated, EPI therapeutic and EPI toxic dose-treated samples compared to control, respectively. For several genes, gene expressions changed compatibly reflecting the DNA methylation regulation. CONCLUSIONS: , have been implicated in different cardiac dysfunction mechanisms. Together with other differentially methylated genes, these genes can be candidates for further investigations of EPI-related toxic mechanisms. Data Repository: The data has been generated by the HeCaToS project (http://www.ebi.ac.uk/biostudies) under accession numbers S-HECA433 and S-HECA434 for the MeDIP-seq data and S-HECA11 for the RNA-seq data. The R code is available on Github (https://github.com/NhanNguyen000/MeDIP).
No takes yet. Share an insight, caveat, or question.
Nguyen et al. (2022) studied Epirubicin-induced cardiotoxicity. Epirubicin vs. 0.1% DMSO (control) was evaluated on Differentially methylated genes (DMRs) with absolute log2 fold change ≥0.5. Epirubicin exposure in human cardiac microtissues significantly altered DNA methylation profiles, identifying 35 candidate genes with strong methylation alterations implicated in cardiac dysfunction.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: