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学科主题: 基础医学
题名:
Aberrant expression of microRNA 155 may accelerate cell proliferation by targeting sex-determining region Y box 6 in hepatocellular carcinoma
作者: Xie, Qing1,2; Chen, Xiangmei1,2; Lu, Fengmin1,2; Zhang, Ting1,2; Hao, Meili1,2,3; Wang, Yongfeng1,2; Zhao, Jingmin4; McCrae, Malcolm A.5; Zhuang, Hui1,2
关键词: hepatocellular carcinoma ; microRNA ; miR-155 ; p53 ; p21waf1 ; cip1
刊名: CANCER
发表日期: 2012-05-01
DOI: 10.1002/cncr.26566
卷: 118, 期:9, 页:2431-2442
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]: CANCER ; MOUSE ; RNA ; MIR-155 ; CATENIN
英文摘要:

BACKGROUND: Recent research has suggested that the oncomir microRNA 155 (miR-155) is up-regulated in hepatocellular carcinoma (HCC). In this study, the authors investigated the tumorigenic mechanism of this oncomir in the development of HCC. METHODS: Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was conducted to analyze the expressions of miR-155 and its potential target genes in paired tumor tissues and adjacent tumor-free tissues and in disease-free liver tissue samples. The in silico predicted target genes of miR-155 were assessed by dual-luciferase reporting assay, real-time RT-PCR, and Western blot analyses. U6 promoters that drive miR-155 precursor overexpression and miR-155 tough decoy knock-down constructs were used to study its affects on cell proliferation in vitro and on tumor formation in nude mice. RESULTS: Quantitative RT-PCR demonstrated a gradual ascension of miR-155 expression in cirrhotic liver tissues and in HCC tumor tissues compared with low expression levels in normal liver tissues. Ectopic expression of miR-155 in HepG2 cells enhanced its tumorigenesis, whereas depletion of the endogenous miR-155 reversed these tumorigenic properties. Ectopic expression of sex-determining region Y box 6 (SOX6) was able to reverse the growth-promoting property of miR-155. Concordantly, the results demonstrated for the first time that SOX6 is a direct target of miR-155. Further analysis revealed that SOX6 reduced cell growth by up-regulating p21waf1/cip1 expression in a p53-dependent manner. In addition, a decline in p21waf1/cip1 expression caused by miR-155 could be reversed by SOX6 expression. CONCLUSIONS: The current data indicated that SOX6 is a novel target of miR-155 and that miR-155 enhances liver cell tumorigenesis at least in part through the novel miR-155/SOX6/p21waf1/cip1 axis. These findings suggest that miR-155 may be a potential target for HCC treatment. Cancer 2012; 118: 2431-42. (C) 2011 American Cancer Society.

语种: 英语
所属项目编号: 2012ZX10002-007 ; 30771099
项目资助者: National S& ; T Major Project for Infectious Diseases Control ; Natural Science Foundation ; University of Massachusetts Medical School
WOS记录号: WOS:000303044600013
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58232
Appears in Collections:基础医学院_病原生物学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Ctr Infect Dis, Beijing 100191, Peoples R China
3.Harbin Med Univ, Dept Microbiol, Harbin, Peoples R China
4.302 Mil Hosp China, Dept Pathol, Beijing, Peoples R China
5.Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England

Recommended Citation:
Xie, Qing,Chen, Xiangmei,Lu, Fengmin,et al. Aberrant expression of microRNA 155 may accelerate cell proliferation by targeting sex-determining region Y box 6 in hepatocellular carcinoma[J]. CANCER,2012,118(9):2431-2442.
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