The histone methyltransferase SMYD2 is a novel therapeutic target for the induction of apoptosis in ovarian clear cell carcinoma cells

  • Oncol Lett. 2020 Nov;20(5):153. doi: 10.3892/ol.2020.12014.
Machiko Kojima  1 ,  Kenbun Sone  1 ,  Katsutoshi Oda  1 ,  Ryuji Hamamoto  2 ,  Syuzo Kaneko  2 ,  Shinya Oki  1 ,  Asako Kukita  1 ,  Akira Kawata  1 ,  Harunori Honjoh  1 ,  Yoshiko Kawata  1 ,  Tomoko Kashiyama  1 ,  Masakazu Sato  1 ,  Ayumi Taguchi  1 ,  Yuichiro Miyamoto  1 ,  Michihiro Tanikawa  1 ,  Tetsushi Tsuruga  1 ,  Kazunori Nagasaka  3 ,  Osamu Wada-Hiraike  1 ,  Yutaka Osuga  1 ,  Tomoyuki Fujii  1
Affiliations
  • 1. Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
  • 2. Division of Molecular Modification and Cancer Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
  • 3. Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Tokyo 173-0003, Japan.
Abstract

Previous studies have suggested that histone methylation can modulate carcinogenesis and Cancer progression. For instance, the Histone Methyltransferase SET and MYND domain containing 2 (SMYD2) is overexpressed in several types of Cancer tissue. The aim of the present study was to determine whether SMYD2 could serve a therapeutic role in ovarian clear cell carcinoma (OCCC). Reverse transcription-quantitative PCR was used to examine SMYD2 expression in 23 clinical OCCC specimens. Moreover, OCCC cell proliferation and cell cycle progression were also examined following small interfering RNA-mediated SMYD2 silencing or treatment with a selective SMYD2 Inhibitor. SMYD2 was significantly upregulated in clinical OCCC specimens, compared with normal ovarian tissue. In addition, SMYD2 knockdown decreased cell viability as determined via a Cell Counting Kit-8 assay. Moreover, the proportion of cells in the sub-G1 phase increased following SMYD2 knockdown, suggesting increased Apoptosis. Treatment with the SMYD2 Inhibitor LLY-507 suppressed OCCC cell viability. These results suggested that SMYD2 could promote OCCC viability, and that SMYD2 inhibition induced Apoptosis in these cells. Thus, SMYD2 inhibitors may represent a promising molecular targeted approach for OCCC treatment.

Keywords
SMYD2; SMYD2 selective inhibitor; epigenetic modification; histone methyltransferase; ovarian clear cell carcinoma.