Expression data from lung SCC treated with DMSO and PXD101. Homo sapiens

We used microarrays to detail the global programme of gene expression in lung SCC cells treated with belinostat, a pan-HDAC inhibitor. The primary focus of this work is to investigate the efficacy of belinostat on lung SCC cells. Our phosphoproteomic profiling analyses revealed the downregulation of MAPK signaling pathway upon drug treatment, together with the induction of apoptosis. While HDAC inhibition generally affects transcription, the mechanism of SOS/MAPK downregulation was therefore proposed to be affected at the transcriptomic level. However, genes related to MAPK pathway were not significantly regulated upon belinostat treatment, whereas ubiquitin-proteasome gene signature was affected. This supports an indirect mechanism of epigenetic regulation on MAPK signaling that should be explored further. Overall design: Lung SCC cell lines treated with DMSO and PXD101 were selected for RNA extraction and hybridization on Affymetrix microarrays. We sought to investigate the initial transcriptomic changes impacted by belinostat at early time point. Cells were treated with belinostat for 8 hours.

本研究采用基因微阵列（microarrays）技术，对经广谱组蛋白去乙酰化酶（pan-HDAC）抑制剂贝利司他（belinostat）处理的肺鳞状细胞癌（lung SCC）细胞的全基因表达谱进行了系统性解析。本研究的核心目标为探究贝利司他对肺SCC细胞的干预效能。通过磷酸化蛋白质组谱分析（phosphoproteomic profiling），我们发现药物处理后丝裂原活化蛋白激酶（MAPK）信号通路出现显著下调，同时诱导了细胞凋亡（apoptosis）。尽管组蛋白去乙酰化酶抑制通常会对转录过程产生广泛影响，但本次研究推测SOS/MAPK通路的下调机制可能作用于转录组水平（transcriptomic level）。然而，经贝利司他处理后，与MAPK通路相关的基因并未出现显著表达变化，而泛素-蛋白酶体基因特征（ubiquitin-proteasome gene signature）则受到明显调控。上述结果支持了表观遗传调控MAPK信号通路的间接作用机制，该机制有待进一步深入研究。实验整体设计：选取经二甲基亚砜（DMSO）与PXD101（贝利司他的研发代号）处理的肺SCC细胞系，提取总RNA后在Affymetrix基因微阵列上进行杂交实验。本研究旨在探究贝利司他在早期时间点对细胞转录组造成的初始改变，实验中细胞经贝利司他处理的时长为8小时。