Abstract
BackgroundNonhistone chromosomal proteins in concert with histones play important roles in the replication and repair of DNA and in the regulation of gene expression. The deregulation of these proteins can contribute to the development of a variety of diseases such as cancer. As a nonhistone chromosomal protein, chromodomain helicase DNA binding protein 5 (CHD5) has recently been identified as the product of a novel tumor suppressor gene (TSG), promoting the transcription of p19ink4a and p16arf. The inactivation of CHD5 was achieved partly through genetic deletion since it is located in 1p36, a region frequently deleted in human tumors. In this study, we aim to study the involvement of CHD5 in gastric cancer, the second most common cancer worldwide.MethodsCHD5 expression in a panel of gastric cancer cells were determined by quantitative RT-PCR. The methylation of CHD5 was evaluated by methylation specific PCR and bisulfite genome sequencing. The effect of CHD5 on growth of gastric cancer cells was tested by colony formation assay.ResultsCHD5 expression was down-regulated in all of gastric cancer cell lines used (100%, 7/7) and significantly restored after pharmacological demethylation. Methylation of CHD5 promoter was detected in all of seven gastric cancer cell lines and in the majority of primary gastric carcinoma tissues examined (73%, 11/15). Finally, ectopic expression of CHD5 in gastric cancer cells led to a significant growth inhibition.ConclusionCHD5 was a TSG epigenetically down-regulated in gastric cancer.
Highlights
Nonhistone chromosomal proteins in concert with histones play important roles in the replication and repair of DNA and in the regulation of gene expression
The ectopic expression of chromodomain helicase DNA binding protein 5 (CHD5) in gastric cancer cells led to a significant growth inhibition
While CHD5 was highly expressed in normal gastric tissues, its expressions were down-regulated in all 7 gastric cancer cell lines (AGS, Kato III, MKN28, MKN45 and NCI-N87 SNU1 and SNU16) (Fig. 1)
Summary
Nonhistone chromosomal proteins in concert with histones play important roles in the replication and repair of DNA and in the regulation of gene expression. The deregulation of these proteins can contribute to the development of a variety of diseases such as cancer. All eukaryotic organisms have developed elaborate ways of packaging DNA into chromatin through the dynamic interactions of various DNA-associated proteins. Nonhistone chromosomal proteins play important roles in the interpretation of histone code by forming chromatin remodeling complexes. Both histones and nonhistone chromosomal proteins are important for the regulation of gene expression, DNA replication and DNA repair. The deregulations in the expression and activity of these proteins could result in the development of a variety of diseases such as cancer [9,10,11,12,13]
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