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

Kojima,Machiko; Sone,Kenbun; Oda,Katsutoshi; Hamamoto,Ryuji; Kaneko,Syuzo; Oki,Shinya; Kukita,Asako; Kawata,Akira; Honjoh,Harunori; Kawata,Yoshiko; Kashiyama,Tomoko; Sato,Masakazu; Taguchi,Ayumi; Miyamoto,Yuichiro; Tanikawa,Michihiro; Tsuruga,Tetsushi; Nagasaka,Kazunori; Wada‑Hiraike,Osamu; Osuga,Yutaka; Fujii,Tomoyuki

doi:10.3892/ol.2020.12014

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

Authors:
- Machiko Kojima
- Kenbun Sone
- Katsutoshi Oda
- Ryuji Hamamoto
- Syuzo Kaneko
- Shinya Oki
- Asako Kukita
- Akira Kawata
- Harunori Honjoh
- Yoshiko Kawata
- Tomoko Kashiyama
- Masakazu Sato
- Ayumi Taguchi
- Yuichiro Miyamoto
- Michihiro Tanikawa
- Tetsushi Tsuruga
- Kazunori Nagasaka
- Osamu Wada‑Hiraike
- Yutaka Osuga
- Tomoyuki Fujii
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Affiliations: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113‑8655, Japan, Division of Molecular Modification and Cancer Biology, National Cancer Center Research Institute, Tokyo 104‑0045, Japan, Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Tokyo 173‑0003, Japan
Published online on: August 24, 2020 https://doi.org/10.3892/ol.2020.12014
Article Number: 153
Copyright: © Kojima et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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