Journal
JOURNAL OF CANCER
Volume 11, Issue 6, Pages 1495-1504Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.36164
Keywords
Neuroblastoma; BARD1; tumor suppressor gene
Categories
Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [20757, 19255]
- Ministero della Salute [GR-2011-02348722]
- Fondazione Italiana per la Lotta al Neuroblastoma
- OPEN Associazione Oncologica Pediatrica e Neuroblastoma
- Regione Campania SATIN grant 2018-2020
- Fondazione Umberto Veronesi post-Doc Fellowship
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BARD1 is associated with the development of high-risk neuroblastoma patients. Particularly, the expression of full length (FL) isoform, FL BARD1, correlates to high-risk neuroblastoma development and its inhibition is sufficient to induce neuroblastoma cells towards a worst phenotype. Here we have investigated the mechanisms of FL BARD1 in neuroblastoma cell lines depleted for FL BARD1 expression. We have shown that FL BARD1 expression protects the cells from spontaneous DNA damage and from damage accumulated after irradiation. We demonstrated a role for FL BARD1 as tumor suppressor to prevent unscheduled mitotic entry of DNA damaged cells and to lead to death cells that have bypassed cell cycle checkpoints. FL BARD1-depleted cells that have survived to checkpoints acquire features of aggressiveness. Overall, our results show that FL BARD1 may defend cells against cancer and prevent malignant transformation of cells.
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