SET7/9 inhibits oncogenic activities through regulation of Gli-1 expression in breast cancer.

Abstract

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.

• Authors: Yongchun Song, Jianli Zhang, Tao Tian, Xiao Fu, Wenjuan Wang, Suoni Li, Tingting Shi, Aili Suo, Zhiping Ruan, Hui Guo, Yu Yao
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 37 Issue 7 Pg. 9311-22 (Jul 2016) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 26779630 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• GLI1 protein, human
• RNA, Messenger
• Zinc Finger Protein GLI1
• Histone-Lysine N-Methyltransferase
• KMT5A protein, human
• SETD7 protein, human

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Blotting, Western
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Movement
• Cell Proliferation
• Female
• Gene Expression Regulation, Neoplastic
• Histone-Lysine N-Methyltransferase (genetics, metabolism)
• Humans
• Immunoenzyme Techniques
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays
• Zinc Finger Protein GLI1 (genetics, metabolism)