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

doi:10.16288/j.yczz.15-128

遗传 ›› 2015, Vol. 37 ›› Issue (9): 918-925.doi: 10.16288/j.yczz.15-128

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

曹继红¹, 廖尉廷², 沃琤¹, 徐国荣¹, 徐焕新¹, 李平龙¹, 陶冶¹, 王鹏¹, 林加日², 邓连瑞³

1. 九江市第三人民医院,九江 332000;
2. 南昌大学转化医学研究院,南昌 330000;
3. 南昌大学第四附属医院,南昌 330000

收稿日期:2015-05-12 修回日期:2015-08-09 出版日期:2015-09-20 发布日期:2015-09-20
通讯作者: 邓连瑞,讲师,研究方向：分子诊断。E-mail: lrdeng@163.com
作者简介:曹继红,副主任医师,专业方向：肝脏疾病。E-mail: caojihong1234@163.com 廖尉廷,本科在读。E-mail: liaoweitingl@163.com曹继红、廖尉廷为并列第一作者。
基金资助:
江西省自然科学基金项目(编号：20122BAB215020)和江西省卫生厅科技计划项目(编号：20143259、20143260)资助

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

Jihong Cao¹, Weiting Liao², Cheng Wo¹, Guorong Xu¹, Huanxin Xu¹, Pinglong Li¹, Ye Tao¹, Peng Wang¹, Jiari Lin², Lianrui Deng³

1. Jiujiang Third People's Hospital, Jiujiang 332000, China;
2. Institute for Translational Medicine, Nanchang University, Nanchang 330000, China;
3. The Second Affiliated Hospital, Nanchang University, Nanchang 330000, China

Received:2015-05-12 Revised:2015-08-09 Online:2015-09-20 Published:2015-09-20

摘要/Abstract

摘要： 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(HepG2)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 siRNA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。

关键词: 组蛋白去乙酰化酶抑制剂, 代谢, 基因表达

Abstract: 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 regulation is still unclear. Here, we integrated the gene expression profiling of HDACIs (TSA and SAHA) in hepatocellular 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.

Key words: HDACIs, metabolism, gene expression

曹继红, 廖尉廷, 沃琤, 徐国荣, 徐焕新, 李平龙, 陶冶, 王鹏, 林加日, 邓连瑞. 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[J]. 遗传, 2015, 37(9): 918-925.

Jihong Cao, Weiting Liao, Cheng Wo, Guorong Xu, Huanxin Xu, Pinglong Li, Ye Tao, Peng Wang, Jiari Lin, Lianrui Deng. Transcriptome screening and verification of genes related to metabolism affected by histone deacetylase inhibitors[J]. HEREDITAS(Beijing), 2015, 37(9): 918-925.

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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

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