The first two authors contributed equally to this article.
Aberrant expression of microRNA 155 may accelerate cell proliferation by targeting sex-determining region Y box 6 in hepatocellular carcinoma†
Article first published online: 11 OCT 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 9, pages 2431–2442, 1 May 2012
How to Cite
Xie, Q., Chen, X., Lu, F., Zhang, T., Hao, M., Wang, Y., Zhao, J., McCrae, M. A. and Zhuang, H. (2012), Aberrant expression of microRNA 155 may accelerate cell proliferation by targeting sex-determining region Y box 6 in hepatocellular carcinoma. Cancer, 118: 2431–2442. doi: 10.1002/cncr.26566
- Issue published online: 20 APR 2012
- Article first published online: 11 OCT 2011
- Manuscript Revised: 15 AUG 2011
- Manuscript Accepted: 15 AUG 2011
- Manuscript Received: 16 APR 2011
- hepatocellular carcinoma;
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.
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.
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.
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. © 2011 American Cancer Society.