| Autor: |
Andrea Marranci, Antonella Prantera, Simona Masotti, Raffaella De Paolo, Caterina Baldanzi, Maurizio S. Podda, Serena Mero, Marianna Vitiello, Cinzia Franchin, Mariavittoria Laezza, Laura Comelli, Giorgio Arrigoni, Tiziana Cervelli, Giovanna Del Pozzo, Laura Poliseno |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Journal of Hematology & Oncology, Vol 16, Iss 1, Pp 1-7 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1756-8722 |
| DOI: |
10.1186/s13045-023-01428-2 |
| Popis: |
Abstract In human cells BRAF oncogene is invariably expressed as a mix of two coding transcripts: BRAF-ref and BRAF-X1. These two mRNA isoforms, remarkably different in the sequence and length of their 3′UTRs, are potentially involved in distinct post-transcriptional regulatory circuits. Herein, we identify PARP1 among the mRNA Binding Proteins that specifically target the X1 3′UTR in melanoma cells. Mechanistically, PARP1 Zinc Finger domain down-regulates BRAF expression at the translational level. As a consequence, it exerts a negative impact on MAPK pathway, and sensitizes melanoma cells to BRAF and MEK inhibitors, both in vitro and in vivo. In summary, our study unveils PARP1 as a negative regulator of the highly oncogenic MAPK pathway in melanoma, through the modulation of BRAF-X1 expression. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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