A regulatory circuit HP1 gamma/miR-451a/c-Myc promotes prostate cancer progression

doi:10.1038/onc.2017.332

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 新药研究国家重点实验室

	A regulatory circuit HP1 gamma/miR-451a/c-Myc promotes prostate cancer progression
	Chang, C.1,7,9; Liu, J.1,7,9 ; He, W.7,9; Qu, M.8; Huang, X.1,7,9 ; Deng, Y.2; Shen, L.1,7,9; Zhao, X.2; Guo, H.2; Jiang, J.3
刊名	ONCOGENE
	2018-01-25
卷号	37 期号:4 页码:415-426
ISSN号	0950-9232
DOI	10.1038/onc.2017.332
文献子类	Article
英文摘要	Heterochromatin protein 1 gamma (HP1 gamma) has been implicated in carcinogenesis of various cancer types. However, the role of HP1 gamma in prostate cancer (PCa) progression and the underlying molecular mechanisms remain largely unknown. We found that HP1 gamma is upregulated in PCa and elevated levels of HP1 gamma in PCa predict poor outcome. In addition, depletion of HP1 gamma in PCa cells not only repressed proliferation and induced apoptosis but also impaired tumorigenicity. We also found that c-Myc was capable of upregulating HP1 gamma by directly binding to the E-box element in the first intron of HP1 gamma gene, and the upregulated HP1 gamma, in turn, repressed the expression of miR-451a by enhancing H3K9 methylation at the promoter region of miR-451a. Furthermore, reduction of miR-451a significantly reversed HP1 gamma loss-induced PCa cell apoptosis, whereas miR-451a overexpression repressed cell survival by targeting and downregulating c-Myc. The association among c-Myc, HP1 gamma and miR-451a was further confirmed in human clinical samples. Therefore, we propose that an HP1 gamma/miR-451a/c-Myc regulatory circuitry exists in PCa cells and this circuit has a crucial role in PCa progression.
资助项目	National Key Research and Development Plan of China[2016YFC0902202] ; National Natural Science Foundation of China[81172009] ; National Natural Science Foundation of China[81672873] ; National Natural Science Foundation of China[81372168] ; National Natural Science Foundation of China[81172442] ; Doctoral Fund of Ministry of Education of China[20110091120028] ; Natural Science Foundation for Universities in Jiangsu Province, China[BK20151396] ; Center for Chronic Disorders of Aging (CCDA) at Philadelphia College of Osteopathic Medicine[00000000] ; 'Personalized Medicines-Molecular Signature-based Drug Discovery and Development', Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020108] ; One Hundred Talent Program of Chinese Academy of Sciences[00000000] ; Program sponsored for Scientific Innovation Research of College Graduate in Jiangsu province[KYZZ_ 0037] ; Open Foundation of State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University[KF-GN-201602] ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM1705KF-02]
WOS关键词	CELL-CYCLE ARREST ; C-MYC ONCOGENE ; HETEROCHROMATIN ; CARCINOMA ; GENES ; HP1-GAMMA ; OVEREXPRESSION ; EXPRESSION ; MICRORNAS ; MIR-451A
WOS研究方向	Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000423331600001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279947]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Yan, J.
作者单位	1.Collaborat Innovat Ctr Genet & Dev, Shanghai, Peoples R China; 2.Nanjing Univ, Nanjing Drum Tower Hosp, Dept Urol, Med Sch,Inst Urol, Nanjing, Jiangsu, Peoples R China; 3.Third Mil Med Univ, Daping Hosp, Inst Surg Res, Dept Urol, Chongqing, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China; 5.Philadelphia Coll Osteopath Med, Dept Biomed Sci, Philadelphia, PA USA; 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 7.Nanjing Univ, Model Anim Res Ctr, MOE Key Lab Model Anim Dis Study, Nanjing, Jiangsu, Peoples R China; 8.Nanjing Univ, Jinling Coll, Sch Chem & Life Sci, Dept Biosci & Bioengn, Nanjing, Jiangsu, Peoples R China; 9.Nanjing Univ, Model Anim Res Ctr, State Key Lab Pharmaceut Biotechnol, Nanjing, Jiangsu, Peoples R China;
推荐引用方式 GB/T 7714	Chang, C.,Liu, J.,He, W.,et al. A regulatory circuit HP1 gamma/miR-451a/c-Myc promotes prostate cancer progression[J]. ONCOGENE,2018,37(4):415-426.
APA	Chang, C..,Liu, J..,He, W..,Qu, M..,Huang, X..,...&Yan, J..(2018).A regulatory circuit HP1 gamma/miR-451a/c-Myc promotes prostate cancer progression.ONCOGENE,37(4),415-426.
MLA	Chang, C.,et al."A regulatory circuit HP1 gamma/miR-451a/c-Myc promotes prostate cancer progression".ONCOGENE 37.4(2018):415-426.