Epigenetic silencing of CHD5, a novel tumor‐suppressor gene, occurs in early colorectal cancer stages

摘要: BACKGROUND Chromodomain helicase DNA binding protein 5 (CHD5) is a family member of chromatin remodeling factors. The epigenetic silencing mechanisms CHD5 in colorectal cancer have not been well studied. METHODS Here we analyzed methylation and mRNA expression vitro clinical samples from African American patients. RNA were isolated formalin fixed paraffin embedded (FFPE) colon tissues. was tested for using methylation-specific polymerase chain reation (PCR) bisulfite sequencing. used quantification qRT-PCR. RKO cell line treated with 5-Aza-dC SAHA. cells also stably transfected CHD5-expressing vector. transcriptional activity studied the 1 kb upstream region promoter dual reporter assay. We performed proliferation, migration, invasion assays line. RESULTS In most adenoma samples, detected contrast to normal In cells, associated repressive histone modifications. restored after treatment reactivation reduced invasion. assay indicated that main regulatory encompassed −489 −823 important sites (TCF/LEF, SP1, AP-2). CONCLUSIONS The gene repressed all types adenomas, either epigenetically or by chromosomal deletion. regulated likely acts as tumor-suppressor early carcinogenesis. Cancer 2014;120:172–180. © 2013 Society.