Please use this identifier to cite or link to this item:
https://doi.org/10.1038/s44319-023-00033-1
DC Field | Value | |
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dc.title | BRD4 isoforms have distinct roles in tumour progression and metastasis in rhabdomyosarcoma. | |
dc.contributor.author | Das, Dipanwita | |
dc.contributor.author | Leung, Jia Yu | |
dc.contributor.author | Balamurugan, Shivaranjani | |
dc.contributor.author | Tergaonkar, Vinay | |
dc.contributor.author | Loh, Amos Hong Pheng | |
dc.contributor.author | Chiang, Cheng-Ming | |
dc.contributor.author | Taneja, Reshma | |
dc.date.accessioned | 2024-02-13T01:11:05Z | |
dc.date.available | 2024-02-13T01:11:05Z | |
dc.date.issued | 2024-01-08 | |
dc.identifier.citation | Das, Dipanwita, Leung, Jia Yu, Balamurugan, Shivaranjani, Tergaonkar, Vinay, Loh, Amos Hong Pheng, Chiang, Cheng-Ming, Taneja, Reshma (2024-01-08). BRD4 isoforms have distinct roles in tumour progression and metastasis in rhabdomyosarcoma.. EMBO Rep. ScholarBank@NUS Repository. https://doi.org/10.1038/s44319-023-00033-1 | |
dc.identifier.issn | 1469-221X | |
dc.identifier.issn | 1469-3178 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/247089 | |
dc.description.abstract | BRD4, a bromodomain and extraterminal (BET) protein, is deregulated in multiple cancers and has emerged as a promising drug target. However, the function of the two main BRD4 isoforms (BRD4-L and BRD4-S) has not been analysed in parallel in most cancers. This complicates determining therapeutic efficacy of pan-BET inhibitors. In this study, using functional and transcriptomic analysis, we show that BRD-L and BRD4-S isoforms play distinct roles in fusion negative embryonal rhabdomyosarcoma. BRD4-L has an oncogenic role and inhibits myogenic differentiation, at least in part, by activating myostatin expression. Depletion of BRD4-L in vivo impairs tumour progression but does not impact metastasis. On the other hand, depletion of BRD4-S has no significant impact on tumour growth, but strikingly promotes metastasis in vivo. Interestingly, BRD4-S loss results in the enrichment of BRD4-L and RNA Polymerase II at integrin gene promoters resulting in their activation. In fusion positive alveolar rhabdomyosarcoma, BRD4-L is unrestricted in its oncogenic role, with no evident involvement of BRD4-S. Our work unveils isoform-specific functions of BRD4 in rhabdomyosarcoma. | |
dc.publisher | Springer Science and Business Media LLC | |
dc.source | Elements | |
dc.subject | Differentiation | |
dc.subject | Epigenetics | |
dc.subject | Integrins | |
dc.subject | Metastasis | |
dc.subject | Myostatin | |
dc.type | Article | |
dc.date.updated | 2024-02-10T08:19:21Z | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.contributor.department | PATHOLOGY | |
dc.contributor.department | PHYSIOLOGY | |
dc.description.doi | 10.1038/s44319-023-00033-1 | |
dc.description.sourcetitle | EMBO Rep | |
dc.published.state | Unpublished | |
Appears in Collections: | Staff Publications Elements |
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File | Description | Size | Format | Access Settings | Version | |
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Das et al Manuscript.pdf | Accepted version | 4.1 MB | Adobe PDF | OPEN | Post-print | Available on 07-07-2024 |
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