Down-regulation of HMGB1 induces apoptosis and inhibits invasion and migration of MCF-7 breast cancer cells through targeting SMARCC1

作者：Ke, Shaobo; Shi, Hongwei; Shi, Wei; Chen, Yongshun^*

来源：International Journal of Clinical and Experimental Pathology, 2017, 10(3): 2764-2773.

• Breast cancer
• HMGB1
• SMARCC1
• apoptosis
• metastasis

High-mobility group box 1 (HMGB1) is a multifunctional protein with intranuclear and extracellular functions associated with most cancers including breast cancer. To investigate the effects of down-regulation of HMGB1 expression, MCF-7 breast cancer cells were infected with HMGB1-specific RNAi lentiviral vectors. The gene silencing effects on HMGB1 expression were subsequently confirmed by RT-PCR and western blotting analyses. HMGB1specific silencing significantly decreased cell proliferation. The impact on proliferation was observed at the cell cycle level-the number of cells in the G2/M phase increased, whereas that in G0/G1 phases decreased. Down-regulation of HMGB1 expression also increased apoptosis of MCF-7 cells, Bax/Bcl-2 ratio and Caspase-3 expression. Finally, silencing of HMGB1 expression significantly resulted in the inhibition of cellular metastatic ability and MMP-9 expression. However, these effects of HMGB1 down-regulation on proliferation, apoptosis, cell cycle and metastasis of MCF-7 cells were significantly inhibited by SMARCC1 overexpression. These findings suggest that HMGB1 is critical for the cellular survival and metastasis of breast cancer and a mechanism referred possibly through targeting SMARCC1, therefore presenting a potential therapeutic target for the treatment of breast cancer.

• 出版日期2017
• 单位武汉大学