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KMID : 0613820190290010105
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Journal of Life Science
2019 Volume.29 No. 1 p.105 ~ p.111
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Effects of an Anti-cancer Drug, Tubastatin A, on the Growth and Development of Immature Oocytes in Mice
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Choi Yun-Jung
Min Gye-Sik
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Abstract
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In recent years, progress has been made in the search for the development of new anti-cancer agents by employing specific inhibitors of histone deacetylase (HDAC)-6 to block signal transduction pathways in cancer cells. This study examined the effects of tubastatin A (TubA), an HDAC-6 inhibitor, on the growth and development of immature oocytes in murine ovaries using RNA sequencing analysis. The results from a gene set enrichment analysis (GSEA) indicated that the expression of most of the gene sets involved in the cell cycle and control and progression of meiosis decreased in the TubA-treated group as compared with that in germinal vesicle (GV) stage oocytes. In addition, an ingenuity pathway analysis (IPA) suggested that TubA not only caused increased expression of p53 and pRB and decreased expression of CDK4/6 and cyclin D but also caused elevated expression of genes involved in the control of the DNA check point in G2/M stage oocytes. These results suggest that TubA may induce cell cycle arrest and apoptosis through the induction of changes in the expression of genes involved in signal transduction pathways associated with DNA damage and the cell cycle of immature oocytes in the ovary.
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KEYWORD
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Histone deacetylase-6, oocyte, ovarian cancer, RNA-sequencing, tubastatin A
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