PXD077277 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Novel Mechanism and Therapy of Anthracycline-Induced Cardiotoxicity (AIC) |
| Description | Anthracyclines are potent chemotherapeutic agents known for their efficacy in treating various cancers via inhibition of topoisomerase II alpha (TOP2A). However, their clinical use is limited due to cardiotoxicity, primarily attributed to off-target inhibition of topoisomerase II beta (TOP2B) in cardiomyocytes. The well-accepted mechanism involves TOP2B inhibition as a key driver of this toxicity. Here, we identify a novel mechanism of anthracycline-induced cardiotoxicity (AIC) involving upregulated TOP2B expression and its direct impact on cardiomyocyte function. Our data show that doxorubicin significantly increased TOP2B protein levels in cardiomyocytes in AIC mouse model. The cardiomyocyte-specific, tamoxifen-inducible TOP2B transgenic mice exhibited pathophysiological features consistent with doxorubicin-induced cardiotoxicity, even without exposure to anthracyclines. Additionally, we discovered that TOP2B binds to SMYD1, a histone methyltransferase critical for muscle cell function. Mutations in SMYD1 are known to cause cardiomyopathy and heart failure in humans, and loss of Smyd1 in mice results in a phenotype resembling AIC. More importantly, TOP2B ASO pretreatment can succussfully prevent the AIC in TOP2B transgenic mice and AIC mouse models. Our findings reveal a novel role for TOP2B in AIC, demonstrating that its upregulation disrupts SMYD1 function in cardiomyocytes, contributing to cardiotoxicity. This study also highlights the therapeutic potential of targeting TOP2B using ASO for preventing AIC in cancer patients, offering new insights into cardioprotective strategies |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-05-05 |
| AnnouncementXML | Submission_2026-05-05_07:46:04.446.xml |
| DigitalObjectIdentifier | https://doi.org/10.6019/PXD077277 |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Belinda Willard |
| SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2026-04-16 21:11:35 | ID requested | |
| ⏵ 1 | 2026-05-05 07:46:05 | announced | |
Publication List
Keyword List
| submitter keyword: TOP2B, SMYD1 |
Contact List
| Jianjun Zhao MD PhD |
|---|
| contact affiliation | Department of Cancer Sciences, Cleveland Clinic, 9500 Euclid Avenue, NE60, Cleveland, OH, 44195, USA. |
| contact email | zhaoj4@ccf.org |
| lab head | |
| Belinda Willard |
|---|
| contact affiliation | Cleveland Clinic |
| contact email | willarb@ccf.org |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD077277
- Label: PRIDE project
- Name: Novel Mechanism and Therapy of Anthracycline-Induced Cardiotoxicity (AIC)
