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学科主题基础医学
Methylation-mediated repression of microRNA 129-2 enhances oncogenic SOX4 expression in HCC
Chen, Xiangmei1,2; Zhang, Ling3; Zhang, Ting1,2; Hao, Meili4; Zhang, Xiaolei1,2; Zhang, Jiangbo1,2; Xie, Qing1,2; Wang, Yongfeng1,2; Guo, Mingzhou5; Zhuang, Hui1,2; Lu, Fengmin1,2
关键词DNA methylation HCC miR-129-2 SOX4 beta-catenin
刊名LIVER INTERNATIONAL
2013-03-01
DOI10.1111/liv.12097
33期:3页:476-486
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Gastroenterology & Hepatology
研究领域[WOS]Gastroenterology & Hepatology
关键词[WOS]HEPATOCELLULAR-CARCINOMA ; CELL-PROLIFERATION ; COLORECTAL-CANCER ; LIVER-CANCER ; IN-VITRO ; METASTASIS ; OVEREXPRESSION ; PATHWAY ; MIR-129 ; GENE
英文摘要

Background & Aims Aberration of miR-129-2 has been linked to a variety of human tumours. However, whether miR-129-2 is involved in hepatocarcinogenesis remains unknown. Here, we investigate the involvement of miR-129-2 in HBV infection-related HCC. Methods A total of 75 paired tumour and their corresponding non-tumour liver tissues from HCC patients with serum HBsAg positive were collected. The methylation of miR-129-2 gene was quantitatively analysed by a DNA methylation-sensitive endonuclease digestion followed by quantitative PCR. The expression of mature miR-129-2 (miR-129-3p) was detected by Taqman RT-PCR. SOX4 expression was detected using quantitative realtime RT-PCR, western blot and immunohistochemical staining. The function of miR-129-2 was investigated using cell proliferation and clonogenicity assays in vitro. Results Compared with the adjacent non-tumour tissues, tumour tissues exhibited significantly increased miR-129-2 hypermethylation both in frequency (37.33% vs. 8%, P<0.0001) and in intensity (14.77% vs. 3.08%, P=0.002). Accordantly, miR-129-3p expression in HCC tissues was significantly lower than that in non-tumour tissues (P=0.0461), in a manner reversely correlated with the level of miR-129-2 hypermethylation. Notably, SOX4 level in the HCC tissues was significantly higher than that in non-tumour tissues (P=0.0174) and normal liver tissues (P=0.0077), correlated reversely with miR-129-3p level (P=0.0105). Furthermore, overexpression of miR-129-2 in HepG2 reduced cell proliferation and clonogenicity, while co-expression with SOX4 could partially reverse its antitumor effects. In addition, SOX4 in HepG2 cell can enhance -catenin/TCF activity by increasing -catenin level. Conclusion The current data indicated that methylation-mediated repression of miR-129-2 may enhance oncogenic SOX4 expression and involve in HCC tumorigenesis.

语种英语
WOS记录号WOS:000314984200018
项目编号2012ZX10002-007 ; 2012ZX10004-904 ; Z111107067311027
资助机构National S & ; T Major Project for Infectious Diseases ; Project of Beijing Municipal Science and Technology Commission
引用统计
被引频次:39[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65205
专题北京大学基础医学院_病原生物学系
北京大学基础医学院
北京大学第三临床医学院_眼科
北京大学临床肿瘤学院_核医学科
作者单位1.Harbin Med Univ, Dept Cell Biol, Harbin, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Sch Basic Med Sci, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Ctr Infect Dis, Sch Basic Med Sci, Beijing 100191, Peoples R China
4.Henan Canc Hosp, Dept Hepatobiliary Surg, Zhengzhou, Peoples R China
5.Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing, Peoples R China
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Chen, Xiangmei,Zhang, Ling,Zhang, Ting,et al. Methylation-mediated repression of microRNA 129-2 enhances oncogenic SOX4 expression in HCC[J]. LIVER INTERNATIONAL,2013,33(3):476-486.
APA Chen, Xiangmei.,Zhang, Ling.,Zhang, Ting.,Hao, Meili.,Zhang, Xiaolei.,...&Lu, Fengmin.(2013).Methylation-mediated repression of microRNA 129-2 enhances oncogenic SOX4 expression in HCC.LIVER INTERNATIONAL,33(3),476-486.
MLA Chen, Xiangmei,et al."Methylation-mediated repression of microRNA 129-2 enhances oncogenic SOX4 expression in HCC".LIVER INTERNATIONAL 33.3(2013):476-486.
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