The histone methyltransferase SMYD2 is a novel therapeutic target for the induction of apoptosis in ovarian clear cell carcinoma cells
The histone methyltransferase SMYD2 is a novel therapeutic target for the induction of apoptosis in ovarian clear cell carcinoma cells
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DOI：
10.3892/ol.2020.12014
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发表时间：
2020-11-01
期刊：
影响因子：
2.9
通讯作者：
Fujii, Tomoyuki
中科院分区：
文献类型：
--
作者：
Kojima, Machiko;Sone, Kenbun;Fujii, Tomoyuki
先前的研究表明，组蛋白甲基化可以调节癌变和癌症进展。例如，组蛋白甲基转移酶SET和含有2的MYND结构域（SMYD2）在几种类型的癌症组织中过度表达。本研究的目的是确定SMYD2是否可以在卵巢透明细胞癌（OCCC）中发挥治疗作用。应用逆转录-定量PCR检测23例临床OCCC标本中SMYD2的表达。此外，在小干扰rna介导的SMYD2沉默或选择性SMYD2抑制剂治疗后，也检测了OCCC细胞增殖和细胞周期进展。与正常卵巢组织相比，临床OCCC标本中SMYD2显著上调。此外，通过细胞计数试剂盒-8测定，SMYD2敲低会降低细胞活力。此外，SMYD2敲低后，亚g(1)期细胞比例增加，提示凋亡增加。SMYD2抑制剂LLY-507抑制OCCC细胞活力。提示SMYD2可促进OCCC细胞活力，抑制SMYD2可诱导OCCC细胞凋亡。因此，SMYD2抑制剂可能是一种很有前途的OCCC分子靶向治疗方法。
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-G(1) 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.