Klin Padiatr 2019; 231(03): 165-166
DOI: 10.1055/s-0039-1687161
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Inhibition of the polycomb repressive complex 1 (PRC1) as a therapeutic option in childhood liver tumors

M Bentrop
1   Department of Pediatric Surgery, University of Munich, Munich, Germany
,
C Vokuhl
2   Institute of Paidopathology, University of Kiel, Kiel, Germany
,
D von Schweinitz
1   Department of Pediatric Surgery, University of Munich, Munich, Germany
,
R Kappler
1   Department of Pediatric Surgery, University of Munich, Munich, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
20 May 2019 (online)

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Introduction:

Hepatoblastoma (HB) is the most common childhood liver tumor. A component of the repressive PRC1 complex has been found to be mutated in some HBs indicating a role in HB biology.

Methods:

After measuring expression levels of different PRC1 components in HB samples via qPCR, we tested the effects of pharmacological PRC1 inhibition on cell proliferation and clonogenic growth of HB cell lines. We performed apoptosis and senescence assays. Expression of possible PRC1 target genes was measured by RNA sequencing.

Results:

We found that the PRC1 component BMI1 is significatly upregulated in HB and higher levels are correlated with metastasis, multifocality and a worse outcome. Pharmacological inhibtion resulted in decreased proliferation and clonogenic growth and increased apoptosis. The BMI1 inhibitor showed strong synergistic effects with cisplatin.

Conclusion:

BMI1 is a promising target for pharmacological inhibition in HB.