https://scholars.lib.ntu.edu.tw/handle/123456789/627185
標題: | SIN3-HDAC complex-associated factor, a chromatin remodelling gene located in the 12p amplicon, is a potential germ cell tumour-specific oncogene | 作者: | Jhuang, Yu-Ling Yang, Chun-Wei Tseng, Yu-Fen Hsu, Chia-Lang Li, Huei-Ying RAY-HWANG YUAN YUNG-MING JENG |
關鍵字: | SINHCAF; belinostat; differentiation; germ cell tumour; histone deacetylase inhibitor; isochromosome 12p; panobinostat; testicular tumour | 公開日期: | 十二月-2022 | 出版社: | WILEY | 卷: | 258 | 期: | 4 | 起(迄)頁: | 353 | 來源出版物: | The Journal of pathology | 摘要: | A genetic hallmark of malignant germ cell tumours (GCTs) is isochromosome 12p, but oncogenes located in 12p that are specifically expressed in GCT have not yet been identified. SIN3-HDAC complex-associated factor (SINHCAF) is a subunit of the Sin3/histone deacetylase (HDAC) complex, and it defines a Sin3a-Hdac complex variant that is required for the self-renewal of mouse embryonic stem cells. This study demonstrated that SINHCAF is expressed in a vast majority of malignant GCTs and is rarely expressed in somatic malignancy. Fluorescence in situ hybridisation revealed SINHCAF amplification in malignant GCTs. SINHCAF silencing using shRNA reduced anchorage-dependent cell proliferation and tumoursphere formation and inhibited tumour cell migration and invasion in GCT cell lines. Moreover, in the GCT cell line NTERA2/D1, SINHCAF silencing inhibited the expression of genes associated with embryonic stem cells and induced the expression of genes associated with neuronal and white fat cell differentiation. Compared with somatic cell lines, GCT cell lines were more susceptible to HDAC inhibitor treatment. Thus, we identified SINHCAF to be a potential oncogene located in the amplicon of chromosome 12p and showed that SINHCAF was specifically expressed in malignant GCTs. HDAC inhibitor treatment may counteract the oncogenic activity of SINHCAF and is a promising therapeutic approach for GCTs. © 2022 The Pathological Society of Great Britain and Ireland. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/627185 | ISSN: | 0022-3417 | DOI: | 10.1002/path.6007 |
顯示於: | 病理學科所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。