title: Epigenetic modifications induced by RGC-32 in colon cancer.
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.
authors.affiliation: Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Vlaicu
authors.forename: Cosmin A
authors.initials: CA
authors.lastname: Tegla
authors.forename: Cornelia D
authors.initials: CD
authors.lastname: Cudrici
authors.forename: Matthew
authors.initials: M
authors.lastname: Fosbrink
authors.forename: Vingh
authors.initials: V
authors.lastname: Nguyen
authors.forename: Philippe
authors.initials: P
authors.lastname: Azimzadeh
authors.forename: Violeta
authors.initials: V
authors.lastname: Rus
authors.forename: Hegang
authors.initials: H
authors.lastname: Chen
authors.forename: Petru A
authors.initials: PA
authors.lastname: Mircea
authors.forename: Abulkalam
authors.initials: A
authors.lastname: Shamsuddin
authors.forename: Horea
authors.initials: H
authors.lastname: Rus
mesh_terms: D000107:Acetylation; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D009124:Muscle Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D018797:Cell Cycle Proteins; D006657:Histones; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C115049:RGCC protein, human