CHD5 is down-regulated through promoter hypermethylation in gastric cancer.
BACKGROUND
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. 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.


METHODS
CHD5 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.


RESULTS
CHD5 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.


CONCLUSIONS
CHD5 was a TSG epigenetically down-regulated in gastric cancer.
Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR, China. wangx118@yahoo.com
Xian
X
Wang
Kenneth K K
KK
Lau
Leo K Y
LK
So
Yun Wah
YW
Lam
D001372:Aza Compounds / Q000737:chemistry; D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004265:DNA Helicases / Q000096:biosynthesis* / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism*; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism
D001372:Aza Compounds; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009419:Nerve Tissue Proteins; D025803:Tumor Suppressor Protein p14ARF; D004265:DNA Helicases; C471926:CHD5 protein, human