期刊
ONCOGENE
卷 33, 期 23, 页码 2978-2986出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2013.262
关键词
SRY; SGF29; c-Myc; STAGA complex; hepatocarcinogenesis
资金
- 'Academic Frontier' project for Private University - MEXT (Ministry of Education, Culture, Sports, Science and Technology)
- Grants-in-Aid for Scientific Research [25870775, 23501271] Funding Source: KAKEN
Sgf29, a component of the SPT-ADA-GCN5 acetyltransferase (SAGA) complex, binds H3K4me2/3 marks and leads to histone H3 acetylation. Previously, we found that downregulation of Sgf29 suppresses c-Myc-mediated malignant transformation. Nonetheless, the upstream regulator of the Sgf29 gene is not yet known. Here, we report that Sry (sex-determining region Y), an HMG (high-mobility group) domain containing transcription factor, directly upregulates Sgf29 gene expression. Sry expression was deregulated in two out of the four tested male rodent hepatocellular carcinoma (rHCC) cell lines. Luciferase reporter and chromatin immunoprecipitation assays indicated that Sry could bind HMG-boxes in the proximal promoter region of the Sgf29 gene. Knockdown of Sry robustly lowered anchorage-independent growth, invasiveness and tumorigenicity of rHCC cells, whereas ectopic expression of Sry conferred more malignant properties. Thus, these data show that Sry is involved in male-specific malignant conversion of rHCCs via Sgf29 upregulation.
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