Sustained cancer‐relevant alternative RNA splicing events driven by PRMT5 in high‐risk neuroblastoma
Protein arginine methyltransferase 5 (PRMT5) is over‐expressed in a wide variety of cancers and is implicated as having a key oncogenic role, achieved in part through its control of the master transcription regulator E2F1. We investigated the relevance of PRMT5 and E2F1 in neuroblastoma (NB) and fou...
| Auteurs principaux: | , , , , , , |
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| Format: | Journal article |
| Langue: | English |
| Publié: |
Wiley Open Access
2024
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| _version_ | 1826313688042176512 |
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| author | Bate‐Eya, LT Albayrak, G Carr, SM Shrestha, A Kanapin, A Samsonova, A La Thangue, NB |
| author_facet | Bate‐Eya, LT Albayrak, G Carr, SM Shrestha, A Kanapin, A Samsonova, A La Thangue, NB |
| author_sort | Bate‐Eya, LT |
| collection | OXFORD |
| description | Protein arginine methyltransferase 5 (PRMT5) is over‐expressed in a wide variety of cancers and is implicated as having a key oncogenic role, achieved in part through its control of the master transcription regulator E2F1. We investigated the relevance of PRMT5 and E2F1 in neuroblastoma (NB) and found that elevated expression of PRMT5 and E2F1 occurs in poor prognosis high‐risk disease and correlates with an amplified Myelocytomatosis viral‐related oncogene, neuroblastoma‐derived (MYCN) gene. Our results show that MYCN drives the expression of splicing factor genes that, together with PRMT5 and E2F1, lead to a deregulated alternative RNA splicing programme that impedes apoptosis. Pharmacological inhibition of PRMT5 or inactivation of E2F1 restores normal splicing and renders NB cells sensitive to apoptosis. Our findings suggest that a sustained cancer‐relevant alternative RNA splicing programme desensitises NB cells to apoptosis, and identify PRMT5 as a potential therapeutic target for high‐risk disease. |
| first_indexed | 2024-09-25T04:18:55Z |
| format | Journal article |
| id | oxford-uuid:717e3ae1-3ac8-41dd-a24d-031f387fe307 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:18:55Z |
| publishDate | 2024 |
| publisher | Wiley Open Access |
| record_format | dspace |
| spelling | oxford-uuid:717e3ae1-3ac8-41dd-a24d-031f387fe3072024-07-27T19:34:10ZSustained cancer‐relevant alternative RNA splicing events driven by PRMT5 in high‐risk neuroblastomaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:717e3ae1-3ac8-41dd-a24d-031f387fe307EnglishJisc Publications RouterWiley Open Access2024Bate‐Eya, LTAlbayrak, GCarr, SMShrestha, AKanapin, ASamsonova, ALa Thangue, NBProtein arginine methyltransferase 5 (PRMT5) is over‐expressed in a wide variety of cancers and is implicated as having a key oncogenic role, achieved in part through its control of the master transcription regulator E2F1. We investigated the relevance of PRMT5 and E2F1 in neuroblastoma (NB) and found that elevated expression of PRMT5 and E2F1 occurs in poor prognosis high‐risk disease and correlates with an amplified Myelocytomatosis viral‐related oncogene, neuroblastoma‐derived (MYCN) gene. Our results show that MYCN drives the expression of splicing factor genes that, together with PRMT5 and E2F1, lead to a deregulated alternative RNA splicing programme that impedes apoptosis. Pharmacological inhibition of PRMT5 or inactivation of E2F1 restores normal splicing and renders NB cells sensitive to apoptosis. Our findings suggest that a sustained cancer‐relevant alternative RNA splicing programme desensitises NB cells to apoptosis, and identify PRMT5 as a potential therapeutic target for high‐risk disease. |
| spellingShingle | Bate‐Eya, LT Albayrak, G Carr, SM Shrestha, A Kanapin, A Samsonova, A La Thangue, NB Sustained cancer‐relevant alternative RNA splicing events driven by PRMT5 in high‐risk neuroblastoma |
| title | Sustained cancer‐relevant alternative RNA splicing events driven by PRMT5 in high‐risk neuroblastoma |
| title_full | Sustained cancer‐relevant alternative RNA splicing events driven by PRMT5 in high‐risk neuroblastoma |
| title_fullStr | Sustained cancer‐relevant alternative RNA splicing events driven by PRMT5 in high‐risk neuroblastoma |
| title_full_unstemmed | Sustained cancer‐relevant alternative RNA splicing events driven by PRMT5 in high‐risk neuroblastoma |
| title_short | Sustained cancer‐relevant alternative RNA splicing events driven by PRMT5 in high‐risk neuroblastoma |
| title_sort | sustained cancer relevant alternative rna splicing events driven by prmt5 in high risk neuroblastoma |
| work_keys_str_mv | AT bateeyalt sustainedcancerrelevantalternativernasplicingeventsdrivenbyprmt5inhighriskneuroblastoma AT albayrakg sustainedcancerrelevantalternativernasplicingeventsdrivenbyprmt5inhighriskneuroblastoma AT carrsm sustainedcancerrelevantalternativernasplicingeventsdrivenbyprmt5inhighriskneuroblastoma AT shresthaa sustainedcancerrelevantalternativernasplicingeventsdrivenbyprmt5inhighriskneuroblastoma AT kanapina sustainedcancerrelevantalternativernasplicingeventsdrivenbyprmt5inhighriskneuroblastoma AT samsonovaa sustainedcancerrelevantalternativernasplicingeventsdrivenbyprmt5inhighriskneuroblastoma AT lathanguenb sustainedcancerrelevantalternativernasplicingeventsdrivenbyprmt5inhighriskneuroblastoma |