| Title | Aberrant expression of microRNA 155 may accelerate cell proliferation by targeting sex-determining region Y box 6 in hepatocellular carcinoma |
| Authors | Xie, Qing Chen, Xiangmei Lu, Fengmin Zhang, Ting Hao, Meili Wang, Yongfeng Zhao, Jingmin McCrae, Malcolm A. Zhuang, Hui |
| Affiliation | Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100191, Peoples R China. Peking Univ, Hlth Sci Ctr, Ctr Infect Dis, Beijing 100191, Peoples R China. Harbin Med Univ, Dept Microbiol, Harbin, Peoples R China. 302 Mil Hosp China, Dept Pathol, Beijing, Peoples R China. Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England. Peking Univ, Hlth Sci Ctr, Dept Microbiol, 38 Xueyuan Rd, Beijing 100191, Peoples R China. |
| Keywords | hepatocellular carcinoma microRNA miR-155 p53 p21waf1 cip1 CANCER MOUSE RNA MIR-155 CATENIN |
| Issue Date | 2012 |
| Publisher | cancer am cancer soc |
| Citation | CANCER.2012,118,(9),2431-2442. |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/193831 |
| ISSN | 0008-543X |
| DOI | 10.1002/cncr.26566 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 医学部待认领 |
