CHD5 is down-regulated through promoter hypermethylation in gastric cancer

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.

Role of annexin A6 in cancer

“…The downregulation of AnxA6 in GC cells is a result of the methylation of its promoter region, as indicated by the fact that a typical CpG island (CGI) in the promoter region of the ANXA6 gene was observed to be methylated in a number of GC cell lines. Furthermore, the expression of AnxA6 may be restored following demethylation treatment (30). The methylation of AnxA6 in GC cells was closely associated with yin yang 1 (YY1), a transcription factor involved in the initiation and maintenance of DNA methylation (30).…”

“…A study by Wang et al (30) indicated that the mRNA levels of AnxA6 were downregulated in GC cell lines and primary gastric carcinoma tissues compared with stomach epithelium cells and normal paracancerous tissues, respectively. Restored expression of AnxA6 in MKN28 cells inhibited their growth and clonogenic ability through inhibiting Ras/MAPK activity.…”

“…It has been implicated as a potential marker for cervical cancer (CC) (25), and as a tumor suppressor in melanoma (26), epithelial carcinoma (23,(27)(28)(29), breast cancer (BC) (23,28), gastric cancer (GC) (30), prostate cancer (PCa) (31,32) and chronic myeloid leukemia (CML) (33). Furthermore, AnxA6 is considered to act as a promoting factor in the cellular adhesion, motility and invasiveness of BC (34,35), the progression of acute lymphoblastic leukemia (ALL) (36), the adhesion of lymphoma (37), and the secretory processes in myeloma cells (21).…”

Homeobox D10 Gene, a Candidate Tumor Suppressor, Is Downregulated through Promoter Hypermethylation and Associated with Gastric Carcinogenesis

“…Thus, identification of novel TSGs inactivated by promoter methylation will be of great importance in understanding the progression of gastric cancer, and could be utilized as biomarkers for the early detection of cancer (7)(8)(9). We and others have found that zinc finger of the cerebellum (ZIC1), fructose-1, 6-bisphosphatase-1 (FBP1), chromodomain helicase DNA binding protein 5 (CHD5), protocadherin 10, and Klotho genes were silenced epigenetically in gastric cancer (10)(11)(12)(13)(14). In the current study, we demonstrate HoxD10 as another important TSGs which undergoes epigenetic modification.…”

Decreased expression of the CHD5 gene and its clinicopathological significance in breast cancer: Correlation with aberrant DNA methylation

“…Furthermore, it also has been reported that aberrant CHD5 promoter methylation was detected in gastric, colorectal, ovarian and lung cancer (20)(21)(22)(23). However, to the best of our knowledge, the role of CHD5 promoter methylation status in breast cancer has not been evaluated.…”