SET7/9 inhibits oncogenic activities through regulation of Gli-1 expression in breast cancer
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SET7/9 is a protein lysine methyltransferase that had been initially identified as a histone lysine methyltransferase which generates monomethylation at histone 3 lysine 4. Different functions were attributed to the protein methylation mediated by SET7/9. In this study, we found that the expression of SET7/9 declined in a majority of the human breast cancer tissues examined compared with normal tissues. Knockdown of SET7/9 promoted the proliferation, migration, and invasion of breast cancer cells. Knockdown of SET7/9 also increased the tumorigenicity of breast cancer cells in vivo. On the contrary, overexpression of SET7/9 in breast cancer cells inhibited these processes. Microarray analysis indicated that Gli-1 may play function as a downstream factor of SET7/9. Overexpression of SET7/9SET7/9 inhibits Gli-1 expression. While knockdown of SET7/9 promotes the expression of Gli-1. Gli-1 inhibited by cyclopamine blocked knockdown SET7/9-driven proliferation, migration, and invasion in breast cancer cell. Furthermore, Gli-1 expression in human breast cancer tissues is negatively correlated with SET7/9 expression. Together, these results helped to realize the antioncogene functions of SET7/9 in breast cancer cells and provided a novel direction to treat breast cancer.
KeywordsSET7/9 Breast cancer Gli-1 Proliferation
The present study was supported by the Scientific and technological research projects of Shaanxi (Grant no. 2013 K12-12-03)
Compliance with ethical standards
This study was approved by the ethics committee of First Affiliated Hospital of Xi’an Jiaotong University.
Conflicts of interest
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