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学科主题: 临床医学
题名:
Silencing NKD2 by promoter region hypermethylation promotes gastric cancer invasion and metastasis by up-regulating SOX18 in human gastric cancer
作者: Jia, Yan1,2,3; Cao, Baoping1,4; Yang, Yunsheng1; Linghu, Enqiang1; Zhan, Qimin5,6; Lu, Youyong7; Yu, Yingyan8; Herman, James G.9; Guo, Mingzhou1
关键词: NKD1 ; NKD2 ; SOX18 ; DNA methylation ; gastric cancer
刊名: ONCOTARGET
发表日期: 2015-10-20
卷: 6, 期:32, 页:33470-33485
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Cell Biology
研究领域[WOS]: Oncology ; Cell Biology
关键词[WOS]: MICROSATELLITE INSTABILITY ; HEPATOCELLULAR-CARCINOMA ; COLORECTAL-CANCER ; BREAST-CARCINOMA ; EPITHELIAL-CELLS ; TUMOR-SUPPRESSOR ; HETEROZYGOSITY ; NAKED2 ; EXPRESSION ; METHYLATION
英文摘要:

Naked cuticle homolog2 (NKD2) is located in chromosome 5p15.3, which is frequently loss of heterozygosity in human colorectal and gastric cancers. In order to understand the mechanism of NKD2 in gastric cancer development, 6 gastric cancer cell lines and 196 cases of human primary gastric cancer samples were involved. Methylation specific PCR (MSP), gene expression array, flow cytometry, transwell assay and xenograft mice model were employed in this study. The expression of NKD1 and NKD2 was silenced by promoter region hypermethylation. NKD1 and NKD2 were methylated in 11.7% (23/196) and 53.1% (104/196) in human primary gastric cancer samples. NKD2 methylation is associated with cell differentiation, TNM stage and distant metastasis significantly (all P < 0.05), and the overall survival time is longer in NKD2 unmethylated group compared to NKD2 methylated group (P < 0.05). Restoration of NKD2 expression suppressed cell proliferation, colony formation, cell invasion and migration, induced G2/M phase arrest, and sensitized cancer cells to docetaxel. NKD2 inhibits SOX18 and MMP-2,7,9 expression and suppresses BGC823 cell xenograft growth. In conclusion, NKD2 methylation may serve as a poor prognostic and chemo-sensitive marker in human gastric cancer. NKD2 impedes gastric cancer metastasis by inhibiting SOX18.

语种: 英语
所属项目编号: 2012CB934002 ; 2015CB553904 ; SS2012AA020314 ; SS2012AA020821 ; SS2012AA020303 ; 2011YQ03013405 ; 81402345 ; 81121004 ; 81161120432 ; 81490753 ; 81401950 ; 14JCQNJC12400 ; 20120115
项目资助者: National Basic Research Program of China (973 Program) ; National High-tech R&amp ; D Program of China (863 Program) ; National Key Scientific Instrument Special Programme of China ; National Science Foundation of China (NSFC) ; Tianjin Research Program of Application Foundation &amp ; Advanced Technology ; Science and Technology Development Program of Tianjin High School
WOS记录号: WOS:000363186600103
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61925
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Key Lab Canc Prevent & Therapy, Tianjin 300060, Peoples R China
2.Nankai Univ, Coll Med, Tianjin 300071, Peoples R China
3.Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing 100853, Peoples R China
4.Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc, Dept Breast Oncol, Tianjin 300060, Peoples R China
5.Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100021, Peoples R China
6.Peking Union Med Coll, Beijing 100021, Peoples R China
7.Peking Univ, Canc Hosp Inst, Key Lab Carcinogenesis & Translat Res, Lab Mol Oncol,Minist Educ, Beijing 100142, Peoples R China
8.Shanghai Jiao Tong Univ, Shanghai Ruijin Hosp, Sch Med, Shanghai 200240, Peoples R China
9.Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA

Recommended Citation:
Jia, Yan,Cao, Baoping,Yang, Yunsheng,et al. Silencing NKD2 by promoter region hypermethylation promotes gastric cancer invasion and metastasis by up-regulating SOX18 in human gastric cancer[J]. ONCOTARGET,2015,6(32):33470-33485.
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