Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells

doi:10.1038/s41419-020-03130-4

	Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells
	Zhang, Xiaojing 1; Peng, Yin 1; Yuan, Yuan 1; Gao, Yuli 1; Hu, Fan 1; Wang, Jian 1; Zhu, Xiaohui 1; Feng, Xianling 1; Cheng, Yulan 2,3; Wei, Yanjie 4
刊名	CELL DEATH & DISEASE
	2020-10-30
卷号	11 期号:10 页码:15
ISSN号	2041-4889
DOI	10.1038/s41419-020-03130-4
英文摘要	Gastric cancer (GC) is the most common cancer throughout the world. Despite advances of the treatments, detailed oncogenic mechanisms are largely unknown. In our previous study, we investigated microRNA (miR) expression profiles in human GC using miR microarrays. We found miR-192/215 were upregulated in GC tissues. Then gene microarray was implemented to discover the targets of miR-192/215. We compared the expression profile of BGC823 cells transfected with miR-192/215 inhibitors, and HFE145 cells transfected with miR-192/-215 mimics, respectively. SET8 was identified as a proposed target based on the expression change of more than twofold. SET8 belongs to the SET domain-containing methyltransferase family and specifically catalyzes monomethylation of H4K20me. It is involved in diverse functions in tumorigenesis and metastasis. Therefore, we focused on the contributions of miR-192/215/SET8 axis to the development of GC. In this study, we observe that functionally, SET8 regulated by miR-192/215 is involved in GC-related biological activities. SET8 is also found to trigger oncogene-induced senescence (OIS) in GC in vivo and in vitro, which is dependent on the DDR (DNA damage response) and p53. Our findings reveal that SET8 functions as a negative regulator of metastasis via the OIS-signaling pathway. Taken together, we investigated the functional significance, molecular mechanisms, and clinical impact of miR-192/215/SET8/p53 in GC.
资助项目	National Nature Science Foundation of China[81871969] ; National Nature Science Foundation of China[81772592] ; National Natural Youth Science Foundation of China[31601028] ; Planned Science and Technology Project of Shenzhen[JCYJ20170818142852491] ; Planned Science and Technology Project of Shenzhen[JCYJ20190808163801777] ; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases[2019B030301009] ; Medical science and technology research foundation of Guangdong Province[A2019211] ; Medical science and technology research foundation of Guangdong Province[A2018170] ; Startup Fund of Shenzhen University[2018015]
WOS研究方向	Cell Biology
语种	英语
出版者	SPRINGERNATURE
WOS记录号	WOS:000588056100006
内容类型	期刊论文
源URL	[http://119.78.100.204/handle/2XEOYT63/16045]
专题	中国科学院计算技术研究所
通讯作者	Hou, Gangqiang; Jin, Zhe
作者单位	1.Shenzhen Univ, Sch Med, Dept Pathol, Guangdong Key Lab Genome Stabil & Dis Prevent & R, Shenzhen 518060, Guangdong, Peoples R China 2.Johns Hopkins Univ, Sch Med, Dept Med, GI Div, Baltimore, MD 21287 USA 3.Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA 4.Shenzhen Inst Adv Technol, Ctr High Performance Comp, Shenzhen 518000, Guangdong, Peoples R China 5.Howard Univ, Coll Med, Dept Med, Washington, DC 20060 USA 6.Howard Univ, Coll Med, Canc Ctr, Washington, DC 20060 USA 7.Meharry Med Ctr, Dept Med, Nashville, TN 37208 USA 8.Shenzhen Sci & Technol Dev Exchange Ctr, Sci & Technol Bldg, Shenzhen 518055, Guangdong, Peoples R China 9.Kangning Hosp, Dept Med, Image Ctr, Shenzhen 518000, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Xiaojing,Peng, Yin,Yuan, Yuan,et al. Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells[J]. CELL DEATH & DISEASE,2020,11(10):15.
APA	Zhang, Xiaojing.,Peng, Yin.,Yuan, Yuan.,Gao, Yuli.,Hu, Fan.,...&Jin, Zhe.(2020).Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells.CELL DEATH & DISEASE,11(10),15.
MLA	Zhang, Xiaojing,et al."Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells".CELL DEATH & DISEASE 11.10(2020):15.