Besides genetic disorders, dysregulation of epigenetic machinery has been proved to play a crucial role in human carcinogenesis, and the histone methylation/demethylation process has been considered as one of key regulators for this event. In this study, we demonstrate that one of the HMTs, suppressor of variegation 3-9 homolog 2 (SUV39H2), plays pivotal roles in human carcinogenesis. Quantitative real-time PCR revealed that SUV39H2 is aberrantly overexpressed in lung cancer, bladder cancer and multiple myeloma compared with their corresponding normal tissues, and immunohistochemical analysis revealed its positive staining in 251 out of 392 lung cancer cases and 16 of 29 bladder cancer cases, while no significant staining was observed in various normal tissues we examined. cDNA microarray analysis using a number of clinical tissues also confirms overexpression of SUV39H2 in various types of cancer. SUV39H2-specific small interfering RNAs significantly knocked down its expression, and caused the G1 arrest as well as suppression of cancer cell growth. Since SUV39H2 expression was undetectable in the normal tissues, SUV39H2 is considered to be an ideal target for development of tumor-specific therapeutics.

Citation Format: Kembun Sone, Yusuke Nakamura, Ryuji Hamamoto. The histone methyltransferase SUV39H2 is a novel target of anticancer therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5159. doi:10.1158/1538-7445.AM2014-5159