PUBLICATION
The histone acetyltransferase hMOF promotes vascular invasion in hepatocellular carcinoma
- Authors
- Poté, N., Cros, J., Laouirem, S., Raffenne, J., Negrão, M., Albuquerque, M., Bedossa, P., Godinho Ferreira, M., Ait Si Ali, S., Fior, R., Paradis, V.
- ID
- ZDB-PUB-200118-8
- Date
- 2020
- Source
- Liver international : official journal of the International Association for the Study of the Liver 40(4): 956-967 (Journal)
- Registered Authors
- Fior, Rita
- Keywords
- H4K16ac, epigenetics, hMOF, liver cancer, vascular invasion
- MeSH Terms
-
- Animals
- Carcinoma, Hepatocellular*/genetics
- Cell Line, Tumor
- Histone Acetyltransferases/genetics*
- Humans
- Liver Neoplasms*/genetics
- Retrospective Studies
- Zebrafish
- PubMed
- 31943753 Full text @ Liver Int.
Citation
Poté, N., Cros, J., Laouirem, S., Raffenne, J., Negrão, M., Albuquerque, M., Bedossa, P., Godinho Ferreira, M., Ait Si Ali, S., Fior, R., Paradis, V. (2020) The histone acetyltransferase hMOF promotes vascular invasion in hepatocellular carcinoma. Liver international : official journal of the International Association for the Study of the Liver. 40(4):956-967.
Abstract
Background & aims Vascular invasion is a major prognostic factor in hepatocellular carcinoma (HCC). We previously identified histone H4 acetylated on lysine 16 (H4K16ac), a histone modification involved in transcription activation, as a biomarker of microvascular invasion (mVI) in HCC. This study aimed to investigate the role of hMOF, the histone acetyltransferase responsible for H4K16 acetylation, in the process of vascular invasion in HCC.
Methods hMOF expression was assessed by RT-qPCR and immunohistochemistry in a retrospective series of HCC surgical samples, and correlated with the presence of mVI. The functional role of hMOF in HCC vascular invasion was investigated in vitro in HCC cell lines using siRNA, transcriptomic analysis and transwell invasion assay, and in vivo using a Zebrafish embryo xenograft model.
Results We found that hMOF was significantly up-regulated at the protein level in HCC with mVI, compared with HCC without mVI (p <0.01). Transcriptomic analysis showed that hMOF downregulation in HCC cell line lead to significant downregulation of key genes and pathways involved in vascular invasion. These results were confirmed by transwell invasion assay, where hMOF downregulation significantly reduced HCC cells invasion. Finally, hMOF downregulation significantly reduced tumor cells intravasation and metastasis in vivo.
Conclusions Altogether, these results underpin a critical role for hMOF in vascular invasion in HCC, via transcription activation of key genes involved in this process. These data confirm the major role of epigenetic alterations in HCC progression, and pave the way for future therapies targeting hMOF in HCC.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping