DOI: 10.5061/dryad.hdr7sqvs5
title: The mRNA expression changes in neonatal primary mouse ventricular cardiomyocytes treated with epirubicin (2uM)

description: Epirubicin (EPI) is effective in the treatment of malignant cancers, but
 its application is limited by life-threatening cardiotoxicity. Iron
 homeostasis disturbance has been implicated in anthracycline-induced
 cardiotoxicity (AIC), and ferroptosis is involved in AIC which is
 dependent upon intracellular iron. However, the role and exact mechanisms
 of ferroptosis in the pathogenesis of epirubicin-induced cardiotoxicity
 (EIC) remain elusive. In this study, we aimed to investigate mechanisms
 underlying ferroptosis-driven EIC. Epirubicin triggered ferroptosis
 both in vivo and in cultured cardiomyocytes, and pretreatment
 with ferroptosis inhibitor, Ferrostatin-1(Fer-1) alleviates EIC.
 Microarray analysis was performed to screen for potential molecules
 involved in EIC in neonatal primary mouse ventricular cardiomyocytes
 (NMVMs). We found that the transcript level of ATP6V0A2, a subunit of
 vacuolar ATPase (V-ATPase), was significantly downregulated when NMVMs
 were subjected to EPI, which was verified in vivo and in vitro as measured
 by real-time quantitative reverse transcription PCR (qRT-PCR) and
 immunoblotting. Intriguingly, overexpression of ATP6V0A2 effectively
 decreased excessive oxidative stress and lipid-peroxidation accumulation,
 thereby inhibiting ferroptosis and protecting cardiomyocytes against EIC,
 as evidenced by functional, enzymatic, and morphological changes.
 Mechanistically, forced expression of ATP6V0A2 restored lysosomal
 acidification in EPI-treated cardiomyocytes and protected cardiomyocytes
 and mice hearts from ferroptosis-driven EIC. In this study, our data
 elucidate that ferroptosis is involved in EIC, which is ignited by
 ATP6V0A2-dependent lysosomal acidification dysfunction. Our study provides
 a new potential therapeutic target for ameliorating EIC.
description: Total RNA was extracted from NMVMs treated with 2μM EPI for 24
 hours and purified with an RNeasy mini kit (QIAGEN) according to the
 manufacturer's instructions. The microarray analysis was performed
 using Affymetrix GeneChip probe arrays (Thermo Fisher Scientific).
 P-values were adjusted with a false discovery rate of 5%. Controls were
 implemented at each step to ensure data quality.
description: # The mRNA expression changes in neonatal primary mouse ventricular
 cardiomyocytes treated with epirubicin (2uM)
 [https://doi.org/10.5061/dryad.hdr7sqvs5](https://doi.org/10.5061/dryad.hdr7sqvs5) ## Description of the data and file structure File name: **deg.anno.mRNA.xlsx** Variables: * ID: The indicated transcript ID of the mouse. * logFC: log2FC, FC: fold change. * Pvalue: The P-value is the probability of obtaining a result at least as extreme as the one that was observed, given that the null hypothesis is true. A p-value of 0.05 or lower is generally considered statistically significant. * regulation: Whether the gene/transcript is up-regulated, down-regulated, or not regulated. * up: The up-regulation genes in neonatal primary mouse ventricular cardiomyocytes (NMVMs) treated with epirubicin (2μM). * down: The down-regulation genes in NMVMs treated with epirubicin (2μM). * no: The down-regulation genes in NMVMs treated with epirubicin (2μM). * ensembl: The indicated ID of the gene in the ENSEMBL database. * uniport: The indicated ID in the NCBI mouse gene database. * symbol: Gene symbol. * description: The description of the indicated gene. * NC|NC_1, NC|NC_2, NC|NC_3: The relative indicated mRNA expression levels in Control groups (Case1, Case2, Case5). * Case|Case1, Case|Case2, Case|Case5: The relative indicated mRNA expression levels in Test groups (NC_1，NC_2，NC_3).