Oncogenic histone methyltransferase EZH2: A novel prognostic marker with therapeutic potential in endometrial cancer

By Shinya Oki, K. Sone, K. Oda, Ryuji Hamamoto, M. Ikemura, D. Maeda, M. Takeuchi, M. Tanikawa, Mayuyo Mori-Uchino, K. Nagasaka and 10 more. 2017

65 citations recorded by the source corpus.

The histone methyltransferase EZH2, a key epigenetic modifier, is known to be associated with human tumorigenesis. However, the physiological importance of EZH2 and its clinical relevance in endometrial cancer remain unclear. Hence, in the present study, we investigated the expression and function of EZH2 in endometrial cancer. In a quantitative real-time PCR analysis of 11 endometrial cancer cell lines and 52 clinical endometrial cancer specimens, EZH2 was significantly overexpressed in cancer cells and tissues compared to that in corresponding normal control cells and tissues. Kaplan-Meier survival analysis using data of the TCGA RNA-seq database and tissue microarrays (TMAs) indicated that EZH2 overexpression is associated with endometrial cancer prognosis. In addition, knockdown of EZH2 using specific siRNAs resulted in growth suppression and apoptosis induction of endometrial cancer cells, accompanied by attenuation of H3K27 trimethylation. Consistent with these results, treatment with GSK126, a specific EZH2 inhibitor, suppressed endometrial cancer cell growth and decreased the number of cancer cell colonies. Furthermore, GSK126 showed additive effects with doxorubicin or cisplatin, which are conventional drugs for treatment of endometrial cancer. Further studies should explore the therapeutic potential of inhibiting EZH2 in patients with endometrial cancer.

Subfields: Cancer Research, Molecular Biology

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In Molecular Biology

1. Syuzo Kaneko
2. Ryuji Hamamoto
3. Yusuke Nakamura
4. N. Dohmae
5. Takehiro Suzuki
6. Makoto Nakakido

Citations in the corpus

• The histone methyltransferase SMYD2 is a novel therapeutic target for the induction of apoptosis in ovarian clear cell carcinoma cells (2020, background): “and induces apoptosis, suggesting the possibility of a novel molecular target drug in endometrial cancer (10).”