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The mRNA expression changes in neonatal primary mouse ventricular cardiomyocytes treated with epirubicin (2uM)

Cite this dataset

Wang, Junhong et al. (2024). The mRNA expression changes in neonatal primary mouse ventricular cardiomyocytes treated with epirubicin (2uM) [Dataset]. Dryad. https://doi.org/10.5061/dryad.hdr7sqvs5

Abstract

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.

README: The mRNA expression changes in neonatal primary mouse ventricular cardiomyocytes treated with epirubicin (2uM)

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).

Methods

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.

Funding

National Natural Science Foundation of China, Award: NSFC 82170269

National Natural Science Foundation of China, Award: NSFC 81570328

Jiangsu Province Hospital, Award: JSPH-MB-2021-15, Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University) clinical capacity enhancement project

The Open Project of Jiangsu Health Administration and Development Research Center, Award: JSHD2022009