1. Enhanced Expression of EHMT2 Is Involved in the Proliferation of Cancer Cells through Negative Regulation of SIAH112
- Author
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Cho, Hyun-Soo, Kelly, John D, Hayami, Shinya, Toyokawa, Gouji, Takawa, Masahi, Yoshimatsu, Masanori, Tsunoda, Tatsuhiko, Field, Helen I, Neal, David E, Ponder, Bruce AJ, Nakamura, Yusuke, and Hamamoto, Ryuji
- Subjects
Ubiquitin-Protein Ligases ,Nuclear Proteins ,Apoptosis ,Azepines ,Histone-Lysine N-Methyltransferase ,Gene Expression Regulation, Neoplastic ,HEK293 Cells ,Cell Line, Tumor ,Histocompatibility Antigens ,Neoplasms ,Quinazolines ,Humans ,Research Article ,Cell Line, Transformed ,Cell Proliferation - Abstract
EHMT2 is a histone lysine methyltransferase localized in euchromatin regions and acting as a corepressor for specific transcription factors. Although the role of EHMT2 in transcriptional regulation has been well documented, the pathologic consequences of its dysfunction in human disease have not been well understood. Here, we describe important roles of EHMT2 in human carcinogenesis. Expression levels of EHMT2 are significantly elevated in human bladder carcinomas compared with nonneoplastic bladder tissues (P < .0001) in real-time polymerase chain reaction analysis. Complementary DNA microarray analysis also revealed its overexpression in various types of cancer. The reduction of EHMT2 expression by small interfering RNAs resulted in the suppression of the growth of cancer cells and possibly caused apoptotic cell death in cancer cells. Importantly, we show that EHMT2 can suppress transcription of the SIAH1 gene by binding to its promoter region (-293 to +51) and by methylating lysine 9 of histone H3. Furthermore, an EHMT2-specific inhibitor, BIX-01294, significantly suppressed the growth of cancer cells. Our results suggest that dysregulation of EHMT2 plays an important role in the growth regulation of cancer cells, and further functional studies may affirm the importance of EHMT2 as a promising therapeutic target for various types of cancer.
- Published
- 2011