Aberrant expression of microRNA 155 may accelerate cell proliferation by targeting sex-determining region Y box 6 in hepatocellular carcinoma.

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.

• Authors: Qing Xie, Xiangmei Chen, Fengmin Lu, Ting Zhang, Meili Hao, Yongfeng Wang, Jingmin Zhao, Malcolm A McCrae, Hui Zhuang
• Journal: Cancer (Cancer) Vol. 118 Issue 9 Pg. 2431-42 (May 01 2012) ISSN: 1097-0142 [Electronic] United States
• PMID: 21989846 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Cancer Society.

Chemical References

• MIRN155 microRNA, human
• MicroRNAs
• SOX6 protein, human
• SOXD Transcription Factors
• Proto-Oncogene Proteins p21(ras)

Topics

• Animals
• Carcinoma, Hepatocellular (genetics, pathology, virology)
• Cell Line, Tumor
• Cell Proliferation
• Gene Knockdown Techniques
• Hep G2 Cells
• Hepatitis B virus (physiology)
• Humans
• Liver (metabolism)
• Liver Neoplasms (genetics, pathology, virology)
• Mice
• Mice, Nude
• MicroRNAs (metabolism)
• Neoplasm Transplantation
• Proto-Oncogene Proteins p21(ras) (metabolism)
• SOXD Transcription Factors (metabolism)
• Up-Regulation