组蛋白去乙酰化酶抑制剂影响的代谢相关基因的组学筛查及验证

Transcriptome screening and verification of genes related to metabolism affected by histone deacetylase inhibitors

组蛋白去乙酰化酶(Histone deacetylases,HDACs)催化组蛋白去乙酰化,与细胞增殖、分化及凋亡等诸多过程密切相关。HDAC抑制剂(HADC inhibitors,HADCIs)具有潜在的抗肿瘤作用,是近年药物筛查的热点之一。近期研究提示HDAC2可通过影响细胞代谢过程发挥抗肿瘤作用,但各类HDACIs调控代谢过程的机制尚待研究。本研究以肝细胞系(Hep G2)为研究对象,整合比较了两种HDACIs(TSA和SAHA)的表达谱数据。在TSA处理组中,筛查到380个差异表达基因(DEGs)及35个DEGs富集的KEGG通路;SAHA处理组的表达分析印证了大多数DEGs(177/380)和富集通路(23/35)。比较分析发现,在这两类HDACIs共同影响的通路中,近一半通路(9/23)与代谢有关;近1/3共享DEGs(66/177)参与代谢过程。通过HDAC2 si RNA细胞实验证实了TSA和SAHA对代谢基因的影响。本研究结果显示HDACIs在治疗肿瘤等代谢性疾病方面具有潜在的应用价值。

Histone deacetylases （HDACs） are responsible for catalyzing the deacetylation of histones,which closely related to many biological processes such as cell proliferation, differentiation and apoptosis. In recent years, HDAC inhibitors （HADCIs）, with the anti-tumor potential, have been hot-spots of drug screening. Although the latest studies suggested that HDAC2 might influence the metabolism, the mechanism of HDACIs in metabolic regu- lation is still unclear. Here, we integrated the gene expression profiling of HDACIs （TSA and SAHA） in hepatocellu- lar carcinoma cell （HepG2）. The results showed 380 differentially expressed genes （DEGs） and 35 KEGG pathways enriched by DEGs in TSA-treatment group. Most of DEGs （177/380） and KEGG pathways （23/35） from TSA-treatment groups were confirmed by SAHA-treatment. About half of KEGG pathways （9/23） were related to metabolism ,and nearly one third of common DEGs （66/177） were involved in metabolic process. Moreover, HDAC2 siRNA experiment verified the effect of HDACIs on metabolic genes, suggesting that HDACIs potentially present a practical value to prevent tumor and other metabolism-related diseases.