Identification of HDAC9 as a viable therapeutic target for the treatment of gastric cancer

doi:10.1038/s12276-019-0301-8

	Identification of HDAC9 as a viable therapeutic target for the treatment of gastric cancer
	Xiong, Kai 1,2,3; Zhang, Hejun 1,3,4; Du, Yang2,4 ; Tian, Jie2,5,6 ; Ding, Shigang 1,3
刊名	EXPERIMENTAL AND MOLECULAR MEDICINE
	2019-08-26
卷号	51 页码:15
ISSN号	1226-3613
DOI	10.1038/s12276-019-0301-8
通讯作者	Du, Yang(yang.du@ia.ac.cn) ; Tian, Jie(jie.tian@ia.ac.cn) ; Ding, Shigang(dingshigang222@163.com)
英文摘要	Histone deacetylase inhibitors (HDACis) are a new class of anticancer drugs confirmed to have good therapeutic effects against gastric cancer (GC) in preclinical experiments, but most HDACis are non-selective (pan-HDACis), with highly toxic side effects. Therefore, it is necessary to screen HDAC family members that play key roles in GC as therapeutic targets to reduce toxic side effects. In this study, we evaluated the targeting specificity of the HDACi suberoylanilide hydroxamic acid (SAHA) for GC via fluorescence molecular imaging (FMI). In vitro FMI results showed that SAHA had higher binding affinity for GC cells than for normal gastric cells. In vivo FMI of gastric tumor-bearing mice confirmed that SAHA can be enriched in GC tissues. However, there was also a high-concentration distribution in normal organs such as the stomach and lungs, suggesting potential side effects. In addition, we found that among the HDAC family members, HDAC9 was the most significantly upregulated in GC cells, and we verified this upregulation in GC tissues. Further experiments confirmed that knockdown of HDAC9 inhibits cell growth, reduces colony formation, and induces apoptosis and cell cycle arrest. These results suggest that HDAC9 has an oncogenic role in GC. Moreover, HDAC9 siRNA suppressed GC tumor growth and enhanced the antitumor efficacy of cisplatin in GC treatment by inhibiting the proliferation and inducing the apoptosis of GC cells in vitro and in vivo. Our findings suggest that the development of HDAC9-selective HDACis is a potential approach to improve the efficacy of chemotherapy and reduce systemic toxicity.
资助项目	National Key Research and Development Plan of China[2016YFA0201404] ; National Key Research and Development Plan of China[2017YFA0205200] ; National Natural Science Foundation of China[81871514] ; National Natural Science Foundation of China[8187071801] ; National Natural Science Foundation of China[81227901] ; National Natural Science Foundation of China[81470083] ; Strategic Priority Research Program from the Chinese Academy of Sciences[XDB02060010] ; International Innovation Team of CAS[20140491524] ; Beijing Municipal Science & Technology Commission[Z161100002616022]
WOS关键词	HISTONE DEACETYLASES ; CELL-PROLIFERATION ; PHASE-II ; EXPRESSION ; COMBINATION ; VORINOSTAT ; CHEMOTHERAPY ; INHIBITION ; PROGNOSIS ; CISPLATIN
WOS研究方向	Biochemistry & Molecular Biology ; Research & Experimental Medicine
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000482997600001
资助机构	National Key Research and Development Plan of China ; National Natural Science Foundation of China ; Strategic Priority Research Program from the Chinese Academy of Sciences ; International Innovation Team of CAS ; Beijing Municipal Science & Technology Commission
内容类型	期刊论文
源URL	[http://ir.ia.ac.cn/handle/173211/27272]
专题	中国科学院自动化研究所
通讯作者	Du, Yang; Tian, Jie; Ding, Shigang
作者单位	1.Peking Univ, Dept Gastroenterol, Hosp 3, Beijing 100191, Peoples R China 2.Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, State Key Lab Management & Control Complex Syst, Beijing 100190, Peoples R China 3.Beijing Key Lab Helicobacter Pylori Infect & Uppe, Beijing 100191, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100080, Peoples R China 5.Beihang Univ, Beijing Adv Innovat Ctr Big Data Based Precis Med, Sch Med, Beijing 100191, Peoples R China 6.Xidian Univ, Sch Life Sci & Technol, Engn Res Ctr Mol & Neuro Imaging, Minist Educ, Xian 710126, Shaanxi, Peoples R China
推荐引用方式 GB/T 7714	Xiong, Kai,Zhang, Hejun,Du, Yang,et al. Identification of HDAC9 as a viable therapeutic target for the treatment of gastric cancer[J]. EXPERIMENTAL AND MOLECULAR MEDICINE,2019,51:15.
APA	Xiong, Kai,Zhang, Hejun,Du, Yang,Tian, Jie,&Ding, Shigang.(2019).Identification of HDAC9 as a viable therapeutic target for the treatment of gastric cancer.EXPERIMENTAL AND MOLECULAR MEDICINE,51,15.
MLA	Xiong, Kai,et al."Identification of HDAC9 as a viable therapeutic target for the treatment of gastric cancer".EXPERIMENTAL AND MOLECULAR MEDICINE 51(2019):15.