The role of histone deacetylase 7 (HDAC7) in cancer cell proliferation: regulation on c-Myc

doi:10.1007/s00109-010-0701-7

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	The role of histone deacetylase 7 (HDAC7) in cancer cell proliferation: regulation on c-Myc
	Zhu, Caihua; Chen, Qin; Xie, Zuoquan; Ai, Jing; Tong, Linjiang; Ding, Jian; Geng, Meiyu
刊名	JOURNAL OF MOLECULAR MEDICINE-JMM
	2011-03
卷号	89 期号:3 页码:279-289
关键词	HDAC7 c-Myc Cell cycle Senescence Transcription
ISSN号	0946-2716
DOI	10.1007/s00109-010-0701-7
文献子类	Article
英文摘要	Histone deacetylases (HDACs) play fundamental roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation, and apoptosis of cancer cells. Although HDACs are recognized to be closely related to cancer development and altered expression of certain HDACs is observed in tumor samples, the arcane characters of HDACs in tumorigenesis have not been fully illustrated. Herein, we report that HDAC7 is a crucial player in cancer cell proliferation. Knockdown of HDAC7 resulted in significant G(1)/S arrest in different cancer cell lines. Subsequent investigations indicated that HDAC7 silencing blocked cell cycle progression through suppressing c-Myc expression and increasing p21 and p27 protein levels. The ectopic expression of c-Myc in turn antagonized the cell cycle arrest and repressed the elevation of p21 and p27 in HDAC7 silencing setting. Of note, HDAC7 deficiency was further identified to induce cellular senescence program, which was also reversed by c-Myc re-expression. Further chromatin immunoprecipitation assays indicated that HDAC7 directly binds with c-Myc gene and HDAC7 silencing decreased c-Myc mRNA level via reducing histone H3/H4 acetylation and repressing the association of RNA polymerase II (RNAP II) with c-Myc gene. Taken together, our findings highlight for the first time an unrecognized link between HDAC7 and c-Myc and offer a novel mechanistic insight into the contribution of HDAC7 to tumor progression.
资助项目	Natural Science Foundation of China for Innovation Research Group[30721005] ; Natural Science Foundation of China for Distinguished Young Scholars[30725046] ; Chinese Academy of Sciences[KSCX2-YWR-25]
WOS关键词	NEOPLASTIC PHENOTYPE ; INHIBITORS ; EXPRESSION ; APOPTOSIS ; SENESCENCE ; GENE ; TRANSCRIPTION ; ANGIOGENESIS ; INACTIVATION ; ACTIVATION
WOS研究方向	Genetics & Heredity ; Research & Experimental Medicine
语种	英语
出版者	SPRINGER HEIDELBERG
WOS记录号	WOS:000288354100010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278589]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ding, Jian
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhu, Caihua,Chen, Qin,Xie, Zuoquan,et al. The role of histone deacetylase 7 (HDAC7) in cancer cell proliferation: regulation on c-Myc[J]. JOURNAL OF MOLECULAR MEDICINE-JMM,2011,89(3):279-289.
APA	Zhu, Caihua.,Chen, Qin.,Xie, Zuoquan.,Ai, Jing.,Tong, Linjiang.,...&Geng, Meiyu.(2011).The role of histone deacetylase 7 (HDAC7) in cancer cell proliferation: regulation on c-Myc.JOURNAL OF MOLECULAR MEDICINE-JMM,89(3),279-289.
MLA	Zhu, Caihua,et al."The role of histone deacetylase 7 (HDAC7) in cancer cell proliferation: regulation on c-Myc".JOURNAL OF MOLECULAR MEDICINE-JMM 89.3(2011):279-289.