Epigenetic inactivation of SLIT2 in human hepatocellular carcinomas

Recent findings have shown that SLIT2 appears to function as a novel tumor suppressor gene. In addition, hypermethylation of its promoter region has been detected in various cancers, including breast and lung cancer, colorectal carcinoma, and gliomas. Here, we report for the first time that there is...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-01, Vol.379 (1), p.86-91
Main Authors: Jin, Jie, You, Haiyan, Yu, Bin, Deng, Yun, Tang, Ning, Yao, Genfu, Shu, Huiqun, Yang, Shengli, Qin, Wenxin
Format: Article
Language:English
Subjects:
Adenovirus
Azacitidine - pharmacology
Base Sequence
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
Cell Movement
DNA Methylation
DNA Modification Methylases - antagonists & inhibitors
Enzyme Inhibitors
Female
Gene Expression Regulation, Neoplastic
Gene Silencing
Hepatocellular carcinoma
Humans
Intercellular Signaling Peptides and Proteins - genetics
Invasion
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Male
Methylation
Middle Aged
Molecular Sequence Data
Nerve Tissue Proteins - genetics
Promoter Regions, Genetic
SLIT2
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Summary:Recent findings have shown that SLIT2 appears to function as a novel tumor suppressor gene. In addition, hypermethylation of its promoter region has been detected in various cancers, including breast and lung cancer, colorectal carcinoma, and gliomas. Here, we report for the first time that there is epigenetic silencing of SLIT2 in human hepatocellular carcinoma (HCC). Downregulation of SLIT2 was detected in 6 of 8 (75%) HCC cell lines by quantitative real-time RT-PCR (qRT-PCR), and the downregulation of SLIT2 was generally dependent on the degree of methylation at the promoter region. Furthermore, expression of SLIT2 was restored in relatively low-expressing cell lines after treatment with 5-aza-2-deoxycytidine (5-Aza-dC). Downregulation of SLIT2 expression was also detected in 45 of 54 primary HCC samples (83.3%), and the decrease in expression was significantly correlated with CpG island hypermethylation. This decrease of SLIT2 expression was also associated with lymph node metastasis in HCC. Moreover, overexpression of SLIT2 in SMMC-7721 cells induced by recombinant adenovirus suppressed cell growth, migration, and invasion, These results suggest that epigenetic inactivation of SLIT2 in HCC may be important in the development and progression of HCC. Thus, SLIT2 may be useful as a therapeutic target in the treatment of HCC.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.12.022