G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of

doi:10.7150/thno.23824

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of
	Zhang, Jie 2; Wang, Yafang 2; Shen, Yanyan 2; He, Pengxing 1; Ding, Jian2 ; Chen, Yi2
刊名	Theranostics
	2018
卷号	8 期号:10 页码:2884-2895
ISSN号	1838-7640
DOI	10.7150/thno.23824
文献子类	Article
英文摘要	G9a is genetically deregulated in various tumor types and is important for cell proliferation; however, the mechanism underlying G9a-induced carcinogenesis, especially in colorectal cancer (CRC), is unclear. Here, we investigated if G9a exerts oncogenic effects in CRC by increasing polo-like kinase 1 (Plk1) expression. Thus, we further characterized the detailed molecular mechanisms. The role of Plk1 in G9a aberrant CRC was determined by performing different and assays, including assessment of cell growth by performing cell viability assay and assessment of signaling transduction profiles by performing immunoblotting, in the cases of pharmacological inhibition or short RNA interference-mediated suppression of G9a. Detailed molecular mechanisms underlying the effect of G9a on Plk1 expression were determined by performing point mutation analysis, chromatin immunoprecipitation analysis, and luciferase reporter assay. Correlation between G9a and Plk1 expression was determined by analyzing clinical samples of patients with CRC by performing immunohistochemistry. Our study is the first to report a significant positive correlation between G9a and Plk1 levels in 89 clinical samples of patients with CRC. Moreover, G9a depletion decreased Plk1 expression and suppressed CRC cell growth both and , thus confirming the significant correlation between G9a and Plk1 levels. Further, we observed that G9a-induced Plk1 regulation depended on p53 inhibition. G9a dimethylated p53 at lysine 373, which in turn increased Plk1 expression and promoted CRC cell growth. These results indicate that G9a-induced and p53-dependent epigenetic programing stimulates the growth of colon cancer, which also suggests that G9a inhibitors that restore p53 activity are promising therapeutic agents for treating colon cancer, especially for CRC expressing wild-type p53.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266324]
专题	药理学第一研究室
作者单位	1.School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China 2.Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
推荐引用方式 GB/T 7714	Zhang, Jie,Wang, Yafang,Shen, Yanyan,et al. G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of[J]. Theranostics,2018,8(10):2884-2895.
APA	Zhang, Jie,Wang, Yafang,Shen, Yanyan,He, Pengxing,Ding, Jian,&Chen, Yi.(2018).G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of.Theranostics,8(10),2884-2895.
MLA	Zhang, Jie,et al."G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of".Theranostics 8.10(2018):2884-2895.