首页> 外文期刊>International journal of molecular medicine >Systemic cell-cycle suppression by Apicidin, a histone deacetylase inhibitor, in MDA-MB-435 cells.
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Systemic cell-cycle suppression by Apicidin, a histone deacetylase inhibitor, in MDA-MB-435 cells.

机译:组蛋白脱乙酰基酶抑制剂Apicidin对MDA-MB-435细胞的全身细胞周期抑制作用。

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Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of potential anti-cancer agents for the treatment of solid and hematological malignancies. However, the best characterized HDAC function concerns the control of gene expression via the regulation of transcription activation or repression. To understand the genome-wide effects of HDAC inhibition on gene regulation, we performed serial gene expression analyses from 0 to 48 h after treating MDA-MB-435, a melanoma-derived highly metastatic tumor cell line, with Apicidin, a HDAC inhibitor. Combined-transcriptomic analysis of large-scale molecular changes induced by Apicidin resulted in the identification of 631 outlier genes that were continuously up- or down-regulated during the 48 h study period. When the 631 outlier genes were mapped to known biological processes, cell-cycle suppression emerged as the function most elicited by Apicidin. In addition comprehensive negative cell-cycle regulation by Apicidin was dissected using gene expression data and validated by Western blot analysis. We suggest the 631 outlier genes as a characteristic molecular signature for Apicidin, and propose concurrent transcriptional suppression of major components of cell-cycle regulatory circuit as potent anti-tumor mechanism of Apicidin. Genetic elements identified during this study also provide the possibility of novel therapeutic interventions in tumor metastasis.
机译:组蛋白脱乙酰基酶(HDAC)抑制剂正作为令人兴奋的新型潜在抗癌药出现,用于治疗实体和血液恶性肿瘤。但是,最有特色的HDAC功能涉及通过转录激活或抑制的调控来控制基因表达。为了了解HDAC抑制对基因调控的全基因组影响,我们在用HDAC抑制剂Apicidin处理MDA-MB-435(一种黑色素瘤衍生的高度转移性肿瘤细胞系)后0至48小时进行了系列基因表达分析。结合转录组学分析由Apicidin诱导的大规模分子变化,导致鉴定了631个异常基因,这些基因在48小时的研究期内连续上调或下调。当将631个离群基因定位到已知的生物过程中时,细胞周期抑制已成为Apicidin最能激发的功能。另外,使用基因表达数据剖析了Apicidin对细胞周期的全面负调控,并通过Western blot分析进行了验证。我们建议将631个离群基因作为Apicidin的特征性分子特征,并建议同时抑制细胞周期调控电路的主要成分作为Apicidin的有效抗肿瘤机制。在这项研究中确定的遗传因素也为肿瘤转移提供了新的治疗手段。

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