Epigenetic modifications induced by RGC-32 in colon cancer |
| |
Authors: | Sonia I Vlaicu Cosmin A Tegla Cornelia D Cudrici Vingh Nguyen Violeta Rus Petru A Mircea Horea Rus |
| |
Institution: | a Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA b Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, MD, USA c Department of Epidemiology, University of Maryland School of Medicine, Baltimore, MD, USA d Medical Clinic No. 1, Cluj-Napoca, Romania e Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA f Veterans Administration Maryland Health Care System, Baltimore, MD, USA |
| |
Abstract: | First described as a cell cycle activator, RGC-32 is both an activator and a substrate for CDC2. Deregulation of RGC-32 expression has been detected in a wide variety of human cancers. We have now shown that RGC-32 is expressed in precancerous states, and its expression is significantly higher in adenomas than in normal colon tissue. The expression of RGC-32 was higher in advanced stages of colon cancer than in precancerous states or the initial stages of colon cancer. In order to identify the genes that are regulated by RGC-32, we used gene array analysis to investigate the effect of RGC-32 knockdown on gene expression in the SW480 colon cancer cell line. Of the 230 genes that were differentially regulated after RGC-32 knockdown, a group of genes involved in chromatin assembly were the most significantly regulated in these cells: RGC-32 knockdown induced an increase in acetylation of histones H2B lysine 5 (H2BK5), H2BK15, H3K9, H3K18, and H4K8. RGC-32 silencing was also associated with decreased expression of SIRT1 and decreased trimethylation of histone H3K27 (H3K27me3). In addition, RGC-32 knockdown caused a significantly higher percentage of SW480 cells to enter S phase and subsequently G2/M. These data suggest that RGC-32 may contribute to the development of colon cancer by regulating chromatin assembly. |
| |
Keywords: | RGC-32 Colon cancer Gene array Histone Acetylation Methylation |
本文献已被 ScienceDirect 等数据库收录! |
|