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DPY30 is required for the enhanced proliferation, motility and epithelial-mesenchymal transition of epithelial ovarian cancer cells.
International Journal of Molecular Medicine 2018 September 12
Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies and is known to be associated with the accumulation of various genetic and epigenetic alterations. As a member of the human histone‑lysine N‑methyltransferase SETD1A (SET1)/histone‑lysine N‑methyltransferase 2A (MLL) complexes that are required for full SET1/MLL methyltransferase activity, protein dpy‑30 homolog (DPY30) catalyzes histone H3K4 methylation, and its dysfunction has been associated with the occurrence of cancer. Therefore, the present study investigated the role of DPY30 in EOC and the potential association between DPY30 expression and the clinicopathological characteristics of EOC. The expression of DPY30 was examined in EOC tissues and cell lines to identify any correlations between the clinicopathological characteristics of EOC and DPY30 expression, and to determine the effects of DPY30 on EOC cell proliferation, migration and invasion. DPY30 was highly expressed in EOC tissues and cell lines, and high DPY30 expression was significantly associated with notable clinicopathological variables in EOC patients, including International Federation of Gynecology and Obstetrics stage, pathological grade and lymph node metastasis. Functional studies on EOC cell lines demonstrated that DPY30 significantly promoted cell proliferation, migration, and invasion, accelerated cell cycle progression, and promoted epithelial‑mesenchymal transition. Chromatin immunoprecipitation assay results revealed that DPY30 regulates histone H3K4 modification via interaction with the vimentin gene promoter, suggesting that DPY30 promotes the transcription of vimentin. Finally, high expression of DPY30 was significantly associated with reduced survival in patients with EOC. The results indicated that DPY30 may act as an oncogene in EOC and thus represents a potential therapeutic target and prognostic marker in EOC.
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