MOF upregulates the estrogen receptor α signaling pathway by its acetylase activity in hepatocellular carcinoma

被引：14

作者：

Wei, Shan ^{[1
,2
]}

Liu, Wei ^{[1
,2
]}

Sun, Ning ^{[1
,2
]}

Wu, Yi ^{[1
,2
,3
]}

Song, Huijuan ^{[1
,2
]}

Wang, Chunyu ^{[1
,2
]}

Wang, Shengli ^{[1
,2
]}

Zou, Renlong ^{[1
,2
]}

Lin, Lin ^{[1
,2
]}

Zeng, Kai ^{[1
,2
]}

Zhou, Baosheng ^{[1
,2
]}

Wang, Manlin ^{[1
,2
]}

Luan, Ruina ^{[1
,2
]}

Yang, Fan ^{[1
,2
]}

Zhao, Yue ^{[1
,4
]}

机构：

[1] China Med Univ, Dept Cell Biol, Key Lab Cell Biol, Minist Publ Hlth, 77 Puhe Rd, Shenyang 110122, Liaoning, Peoples R China

[2] China Med Univ, Sch Life Sci, Key Lab Med Cell Biol, Minist Educ, 77 Puhe Rd, Shenyang 110122, Liaoning, Peoples R China

[3] Shenyang Med Coll, Dept Pathogen Biol, Shenyang, Peoples R China

[4] Liao Ning Tumor Hosp, Dept Mol Oncol, Shenyang, Peoples R China

来源：

CANCER SCIENCE | 2021年 / 112卷 / 05期

基金：

中国国家自然科学基金;

关键词：

acetylation; estrogen receptor α hepatocellular carcinoma; MOF; tumor suppression; EXPRESSION; PROTEIN; CANCER; HMOF; PROLIFERATION; APOPTOSIS; COMPLEX; BINDING; IMPACT; MYST1;

D O I：

10.1111/cas.14836

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The histone acetyltransferase MOF (KAT8) is mainly involved in the acetylation of histone H4 at lysine 16 (H4K16) and some non-histone proteins. The MOF expression level is significantly reduced in many cancers, however the biological function of MOF and its underlying mechanism are still elusive in hepatocellular carcinoma (HCC). Estrogen receptor alpha (ER alpha) has been considered as a tumor suppressor in HCC. Here, we demonstrated that MOF expression is significantly reduced in HCC samples, and is positively correlated with that of ER alpha. MOF interacts with ER alpha, and participates in acetylation of ER alpha at K266, K268, K299, thereby inhibiting ER alpha ubiquitination to maintain the stability of ER alpha. In addition, MOF participates in the upregulation of ER alpha-mediated transactivation. Depletion of MOF significantly promotes cell growth, migration, and invasion in HCC cell lines. Taken together, our results provide new insights to understand the mechanism underlying the modulation function of MOF on ER alpha action in HCC, suggesting that MOF might be a potential therapeutic target for HCC.

引用

页码：1865 / 1877

页数：13

共 39 条

[21] A novel IFNα-induced long noncoding RNA negatively regulates immunosuppression by interrupting H3K27 acetylation in head and neck squamous cell carcinoma [J].