Transcriptomics

Dataset Information

0

Phosphodiesterase 10A inactivation protects against doxorubicin-induced cardiotoxicity and concomitantly inhibits tumor growth


ABSTRACT: Phosphodiesterase 10A (PDE10A), by degrading cAMP/cGMP, play critical roles in cardiovascular biology/disease. Cardiotoxicity is a clinical complication of chemotherapy. We aim to determine the role of PDE10A in cancer growth and cardiotoxicity induced by doxorubicin (DOX), a chemotherapy drug. We found that PDE10A deficiency/inhibition alleviated DOX-induced cardiotoxicity in C57Bl/6J mice, including myocardial atrophy, apoptosis, and dysfunction. RNAseq study revealed several PDE10A-regulated signaling associated with DOX-induced cardiotoxicity. In cancer cells, PDE10A inhibition increased the death, decreased the proliferation, and potentiated the effect of DOX in various cancer-cell lines. Importantly, in nude mice with implanted ovarian cancer xenografts, PDE10A inhibition attenuated tumor growth while protected against DOX-induced cardiotoxicity. In isolated cardiomyocytes (CMs), PDE10A contributed to DOX-induced CM death via promoting mitochondrial dysfunction, and to CM atrophy via potentiating foxo3 signaling. Collectively, our study elucidates a novel role for PDE10A in cardiotoxicity and cancer growth in vitro and in vivo, and suggest that PDE10A inhibition may represent a novel strategy in cancer therapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE224157 | GEO | 2023/06/22

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2016-10-30 | GSE74513 | GEO
2024-09-07 | GSE242692 | GEO
2023-06-03 | GSE233644 | GEO
2021-12-29 | GSE178887 | GEO
| PRJNA765675 | ENA
2020-01-01 | GSE121275 | GEO
2023-03-11 | PXD025633 | Pride
2022-02-17 | PXD029795 | Pride
2024-06-20 | GSE247345 | GEO
2017-12-04 | GSE97642 | GEO