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P300-dependent acetylation of histone H3 is required for epidermal growth factor receptor-mediated high-mobility group protein A2 transcription in hepatocellular carcinoma.

Authors :
Liang C
Niu J
Wang X
Zhang ZS
Yang RH
Yao X
Liu FY
Li WQ
Pei SH
Sun H
Wang CJ
Fang D
Xie SQ
Source :
Cancer science [Cancer Sci] 2021 Feb; Vol. 112 (2), pp. 679-690. Date of Electronic Publication: 2020 Dec 15.
Publication Year :
2021

Abstract

High-mobility group protein A2 (HMGA2) is highly expressed in hepatocellular carcinoma (HCC) cells and contributes to tumor metastasis and poor patient survival. However, the molecular mechanism through which HMGA2 is transcriptionally regulated in HCC cells remains largely unclear. Here, we showed that the expression HMGA2 was upregulated in HCC, and that elevated HMGA2 could promote tumor metastasis. Incubation of HCC cells with epidermal growth factor (EGF) could promote the expression of HMGA2 mRNA and protein. Mechanistic studies suggested that EGF can phosphorylate p300 at Ser1834 residue through the PI3K/Akt signaling pathway in HCC cells. Knockdown of p300 can reverse EGF-induced HMGA2 expression and histone H3-K9 acetylation, whereas a phosphorylation-mimic p300 S1834D mutant can stimulate HMGA2 expression as well as H3-K9 acetylation in HCC cells. Furthermore, we identified that p300-mediated H3-K9 acetylation participates in EGF-induced HMGA2 expression in HCC. In addition, the levels of H3-K9 acetylation positively correlated with the expression levels of HMGA2 in a chemically induced HCC model in rats and human HCC specimens.<br /> (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Details

Language :
English
ISSN :
1349-7006
Volume :
112
Issue :
2
Database :
MEDLINE
Journal :
Cancer science
Publication Type :
Academic Journal
Accession number :
33164305
Full Text :
https://doi.org/10.1111/cas.14729