The histone acetyltransferase hMOF promotes vascular invasion in hepatocellular carcinoma

Autor: Pierre Bedossa, Magda Negrão, Jerome Raffenne, Jérôme Cros, Miguel Godinho Ferreira, Rita Fior, Nicolas Poté, Samira Laouirem, Valérie Paradis, Slimane Ait Si Ali, Miguel Albuquerque
Přispěvatelé: GODINHO FERREIRA, Miguel, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Pathologie [Hôpital Beaujon - APHP], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Champalimaud Foundation [Lisbon, Portugal], Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université Nice Sophia Antipolis (... - 2019) (UNS)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
PVS
CHT
[SDV]Life Sciences [q-bio]
Cell
microvascular invasion
perivitelline space
FBS
0302 clinical medicine
HCC
Zebrafish
ComputingMilieux_MISCELLANEOUS
Histone Acetyltransferases
fetal bovine serum
biology
Liver Neoplasms
human ortholog of Males absent On the First
hepatocellular carcinoma
3. Good health
[SDV] Life Sciences [q-bio]
HPF
Histone
medicine.anatomical_structure
histone H4 acetylated on lysine 16
030220 oncology & carcinogenesis
Ingenuity Pathway Analysis
030211 gastroenterology & hepatology
HPI
hours post-injection
Carcinoma
Hepatocellular
hMOF
[SDV.CAN]Life Sciences [q-bio]/Cancer
caudal haematopoietic tissue
Histone H4
liver cancer
03 medical and health sciences
mVI
Gentamicin protection assay
Downregulation and upregulation
[SDV.CAN] Life Sciences [q-bio]/Cancer
Cell Line
Tumor
medicine
Animals
Humans
Epigenetics
quantitative real-time PCR
vascular invasion
neoplasms
Retrospective Studies
Hepatology
epigenetics
Intravasation
qRT-PCR
Histone acetyltransferase
small interfering RNA
digestive system diseases
IPA
siRNA
Cancer research
biology.protein
H4K16ac
hours post-fertilization
Zdroj: Liver International
Liver International, 2020, 40, Epub ahead of print. ⟨10.1111/LIV.14381⟩
Liver International, Wiley-Blackwell, 2020, 40 (4), pp.956-967. ⟨10.1111/liv.14381⟩
Liver International, Wiley-Blackwell, 2020, 40, Epub ahead of print. ⟨10.1111/LIV.14381⟩
ISSN: 1478-3223
1478-3231
DOI: 10.1111/LIV.14381⟩
Popis: International audience; BACKGROUND & AIMS:Vascular invasion is a major prognostic factor in hepatocellular carcinoma (HCC). We previously identified histone H4 acetylated at 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 upregulated at the protein level in HCC with mVI, compared with HCC without mVI (P < .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 tumour cell 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.
Databáze: OpenAIRE
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