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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.
- 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.)
- Subjects :
- Acetylation
Animals
Carcinoma, Hepatocellular metabolism
ErbB Receptors metabolism
Humans
Liver Neoplasms metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Rats
Rats, Sprague-Dawley
Transcription, Genetic
p300-CBP Transcription Factors metabolism
Carcinoma, Hepatocellular pathology
Gene Expression Regulation, Neoplastic physiology
HMGA2 Protein biosynthesis
Histones metabolism
Liver Neoplasms pathology
Subjects
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