J Cancer 2020; 11(6):1495-1504. doi:10.7150/jca.36164

Research Paper

Functional characterization of full-length BARD1 strengthens its role as a tumor suppressor in neuroblastoma

Flora Cimmino1,2✉, Marianna Avitabile1,2, Vito Alessandro Lasorsa1,2, Lucia Pezone1, Antonella Cardinale1, Annalaura Montella2, Sueva Cantalupo3, Achille Iolascon1,2, Mario Capasso1,2,3

1. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli “Federico II”, Naples, Italy
2. CEINGE Biotecnologie Avanzate, Naples, Italy
3. IRCCS SDN, Naples, Italy

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Citation:
Cimmino F, Avitabile M, Lasorsa VA, Pezone L, Cardinale A, Montella A, Cantalupo S, Iolascon A, Capasso M. Functional characterization of full-length BARD1 strengthens its role as a tumor suppressor in neuroblastoma. J Cancer 2020; 11(6):1495-1504. doi:10.7150/jca.36164. Available from https://www.jcancer.org/v11p1495.htm

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Abstract

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.

Keywords: Neuroblastoma, BARD1, tumor suppressor gene