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H3K4me3是骨化三醇（1α,25(OH)₂D₃）在卵巢癌生物学中抗增殖作用的潜在介导因子。

H3K4me3 Is a Potential Mediator for Antiproliferative Effects of Calcitriol (1α,25(OH)2D3) in Ovarian Cancer Biology.

机构信息

Department of Obstetrics and Gynaecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany.

Department of Obstetrics and Gynaecology, University Hospital Augsburg, Stenglinstr. 2, 86156 Augsburg, Germany.

出版信息

Int J Mol Sci. 2020 Mar 20;21(6):2151. doi: 10.3390/ijms21062151.

DOI:10.3390/ijms21062151
PMID:32245092
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7139961/
Abstract

Posttranslational histone modification plays an important role in tumorigenesis. Histone modification is a dynamic response of chromatin to various signals, such as the exposure to calcitriol (1α,25(OH)D). Recent studies suggested that histone modification levels could be used to predict patient outcomes in various cancers. Our study evaluated the expression level of histone 3 lysine 4 trimethylation (H3K4me3) in a cohort of 156 epithelial ovarian cancer (EOC) cases by immunohistochemical staining and analyzed its correlation to patient prognosis. The influence of 1α,25(OH)D on the proliferation of ovarian cancer cells was measured by BrdU proliferation assay in vitro. We could show that higher levels of H3K4me3 were correlated with improved overall survival (median overall survival (OS) not reached vs. 37.0 months, = 0.047) and identified H3K4me3 as a potential prognostic factor for the present cohort. Ovarian cancer cell 1α,25(OH)D treatment induced H3K4me3 protein expression and exhibited antiproliferative effects. By this, the study suggests a possible impact of H3K4me3 expression on EOC progression as well as its relation to calcitriol (1α,25(OH)D) treatment. These results may serve as an explanation on how 1α,25(OH)D mediates its known antiproliferative effects. In addition, they further underline the potential benefit of 1α,25(OH)D supplementation in context of ovarian cancer care.

摘要

翻译后组蛋白修饰在肿瘤发生中起重要作用。组蛋白修饰是染色质对各种信号的动态反应，如暴露于骨化三醇（1α,25(OH)D）。最近的研究表明，组蛋白修饰水平可用于预测各种癌症患者的预后。我们的研究通过免疫组织化学染色评估了156例上皮性卵巢癌（EOC）病例队列中组蛋白3赖氨酸4三甲基化（H3K4me3）的表达水平，并分析了其与患者预后的相关性。通过体外BrdU增殖试验测量1α,25(OH)D对卵巢癌细胞增殖的影响。我们发现，较高水平的H3K4me3与总体生存率提高相关（中位总生存期（OS）未达到 vs. 37.0个月，P = 0.047），并确定H3K4me3为本队列的潜在预后因素。卵巢癌细胞1α,25(OH)D处理诱导H3K4me3蛋白表达并表现出抗增殖作用。由此，该研究提示H3K4me3表达对EOC进展可能有影响及其与骨化三醇（1α,25(OH)D）治疗的关系。这些结果可能解释了1α,25(OH)D如何介导其已知的抗增殖作用。此外，它们进一步强调了在卵巢癌治疗中补充1α,25(OH)D的潜在益处。

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