Functional role of SIRT1-induced HMGB1 expression and acetylation in migration, invasion and angiogenesis of ovarian cancer

W. Jiang, P. Jiang, R. Yang, D.-F. Liu

Department of Medical, Jinan Maternity and Child Care Hospital, Jinan, Shandong, China. dianfangliuavd@sohu.com

---

• Oncology

OBJECTIVE: Ovarian cancer is a commonly occurred tumor in females. High motility group box-1 protein (HHMB1) is a chromosome-related protein with multiple functions. A recent study revealed critical roles of HMGB1 in occurrence and progression of ovarian cancer. Sirtuin 1 (SIRT1) is a recently identified novel molecule, which regulates acetylation of HMGB1. Whether SIRT1 is involved in migration, invasion or angiogenesis of ovarian cancer is unclear. This study aims to investigate the role of SIRT1-induced HMGB1 acetylation in migration, invasion, and angiogenesis in ovarian cancer.

PATIENTS AND METHODS: In ovarian cancer cell line, SIRT1 expression was potentiated. Western blot and immunofluorescence were used to measure HMGB1 expression, acetylation level, and nuclear translocation. Scratch assay and transwell chamber methods were used to examine cell migration and invasion potency. A mouse model with ovarian cancer cell transplantation was generated to measure induced nitric oxide synthase (iNOs) and CD105 expression.

RESULTS: Compared to adjacent tissues, ovarian cancer tissues had significantly decreased SIRT1 expression. In ovarian cancer cells, SIRT1 over-expression decreased HMGB1 and acetylation levels, and SIRT1 knockdown facilitated HMGB1 expression and acetylation. SIRT1 over-expression also suppressed nuclear translocation of HMGB1. Meanwhile, SIRT1 could suppress, migration and angiogenesis of ovarian cancer cells via HMGB1.

CONCLUSIONS: SIRT1 over-expression effectively inhibited HMGB1 expression and acetylation, thus inhibiting ovarian cancer migration, invasion and angiogenesis. HMGB1 modulated behaviors of ovarian cancer via SIRT1. Therefore, SIRT1 might work as a treatment target for managing ovarian cancer migration.

Free PDF Download