Down-regulation of SIRT3 promotes ovarian carcinoma metastasis
| Autor: | Yu-xia Gao, Li-min Jing, Xue-cai Dong, Wen-xiang Wang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Cell Biophysics Down-Regulation Mice Nude Biochemistry Metastasis 03 medical and health sciences Downregulation and upregulation Cell Movement Ovarian carcinoma Cell Line Tumor Sirtuin 3 medicine Animals Humans Neoplasm Invasiveness Molecular Biology Ovarian Neoplasms Gene knockdown biology Liver Neoplasms Ovary Twist-Related Protein 1 Nuclear Proteins Cell Biology medicine.disease Gene Expression Regulation Neoplastic 030104 developmental biology Histone medicine.anatomical_structure Liver Cancer cell biology.protein Cancer research Female Ovarian cancer |
| Zdroj: | Biochemical and biophysical research communications. 475(3) |
| ISSN: | 1090-2104 |
| Popis: | Distant metastasis and local recurrence are still the major causes for failure of treatment in patients with ovarian carcinoma (OC), making it urgent to further elicit the molecular mechanisms of OC metastasis. Sirtuin-3 (SIRT3), a member of the NAD+-dependent Class III histone deacetylases, may function as different role depending on the cell-type and tumor-type. However, the function and mechanism of SIRT3 has been not explored in OC metastasis. Here, we found that SIRT3 was significantly down-regulated in the metastatic tissues and highly metastatic cell line of ovarian cancer. In addition, knockdown of SIRT3 enhanced the migration and invasion in vitro and the liver metastasis in vivo of ovarian cancer cell. By contrast, ectopic overexpression of SIRT3 dramatically suppressed cancer cell metastatic capability. Mechanistically, SIRT3 inhibits epithelial-to-mesenchymal transition (EMT) by down-regulating Twist in ovarian cancer cells. Furthermore, an interaction between SIRT3 and Twist was detected. In conclusion, our results demonstrated that SIRT3 plays a crucial suppressive role in the metastasis of ovarian cancer by down-regulating Twist, and that this novel SIRT3/Twist axis may be valuable to develop new strategies for treating OC patients with metastasis. |
| Databáze: | OpenAIRE |
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