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学科主题: 临床医学
题名:
SMYD3 as an Oncogenic Driver in Prostate Cancer by Stimulation of Androgen Receptor Transcription
作者: Liu, Cheng1; Wang, Chang1,7,8,9; Wang, Kun1; Liu, Li2,3; Shen, Qi5; Yan, Keqiang1; Sun, Xiaoqing6; Chen, Jie1; Liu, Jikai1; Ren, Hongbo1; Liu, Hainan1; Xu, Zhonghua1; Hu, Sanyuan2; Xu, Dawei4,7,8,9; Fan, Yidong1
刊名: JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
发表日期: 2013-11-01
DOI: 10.1093/jnci/djt304
卷: 105, 期:22, 页:1719-1728
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: HISTONE METHYLTRANSFERASE ; CELL-PROLIFERATION ; EXPRESSION ; INVASION ; GROWTH ; METHYLATION ; PROGRESSION ; LEADS ; SP1
英文摘要:

Androgen receptor (AR) is critical for prostate tumorigenesis and is frequently overexpressed during prostate cancer (PC) progression. However, few studies have addressed the epigenetic regulation of AR expression.

We analyzed SMYD3 expression in human PC with Western blot and immunohistochemistry. SMYD3 expression was knocked down using short hairpin RNA (shRNA) or small interfering RNA (siRNA). Cell proliferation, colony formation, and apoptosis analyses and xenograft transplantation were performed to evaluate the impact of SMYD3 depletion on PC cells. AR expression and promoter activity were determined using real-time quantitative polymerase chain reaction, western blot, and luciferase reporter assay. AR promoter association with Sp1, SMYD3, and histone modifications was assessed by chromatin immunoprecipitation. Differences in AR mRNA abundance and promoter activity were analyzed using Wilcoxon signed-rank tests, SMYD3 expression was analyzed using with MannWhitney U tests for unpaired samples, and tumor weight was analyzed with Student t test. All statistical tests were two-sided.

The upregulation of SMYD3 protein expression was observed in seven of eight prostate tumor specimens, compared with matched normal tissues. Immunohistochemical analysis showed a strong SMYD3 staining in the nuclei of PC tissues in eight of 25 (32%) cases and in the cytoplasm in 23 out of 25 (92%) cases, whereas benign prostate tissue exhibited weak immunostaining. Depletion of SMYD3 by siRNA or shRNA inhibited PC cell proliferation (72 hours relative to 24 hours: control shRNA vs SMYD3 shRNA 1: mean fold change 2.76 vs 1.68; difference 1.08; 95% confidence interval 0.78 to 1.38, P < .001), colony formation, cell migration, invasion, and xenograft tumor formation. Two functional SMYD3-binding motifs were identified in the AR promoter region.

SMYD3 promotes prostate tumorigenesis and mediates epigenetic upregulation of AR expression.

语种: 英语
所属项目编号: 2012CB911202 ; 30901497 ; 81272814 ; 81372765 ; Y2003C08 ; BS2010YY027 ; 2012TS094
项目资助者: National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China ; Shandong Provincial Natural Science Foundation ; Promotive Research Fund for Excellent Young and Middle-Aged Scientists of Shandong Province ; Independent Innovation Foundation of Shandong University ; Swedish Cancer Society ; Swedish Research and Counci ; Cancer Society in Stockholm
WOS记录号: WOS:000327539000009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64473
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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作者单位: 1.Karolinska Univ, Hosp Solna, Ctr Mol Med, Stockholm, Sweden
2.Karolinska Inst, Stockholm, Sweden
3.Peking Univ, Hosp 1, Dept Urol, Beijing 100871, Peoples R China
4.Qingdao Municipal Hosp, Dept Urol, Qingdao, Peoples R China
5.Shandong Univ, Qilu Hosp, Dept Urol, Jinan 250012, Shandong, Peoples R China
6.Shandong Univ, Qilu Hosp, Dept Gen Surg, Jinan 250012, Shandong, Peoples R China
7.Shandong Univ, Qilu Hosp, Sch Nursing, Jinan 250012, Shandong, Peoples R China
8.Shandong Univ, Hosp 2, Cent Res Lab, Jinan 250012, Shandong, Peoples R China
9.Karolinska Univ, Hosp Solna, Dept Med, Div Haematol, Stockholm, Sweden

Recommended Citation:
Liu, Cheng,Wang, Chang,Wang, Kun,et al. SMYD3 as an Oncogenic Driver in Prostate Cancer by Stimulation of Androgen Receptor Transcription[J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE,2013,105(22):1719-1728.
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