Epigenetic modifications induced by RGC-32 in colon cancer.
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.
Vlaicu
Sonia I
SI
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Tegla
Cosmin A
CA
Cudrici
Cornelia D
CD
Fosbrink
Matthew
M
Nguyen
Vingh
V
Azimzadeh
Philippe
P
Rus
Violeta
V
Chen
Hegang
H
Mircea
Petru A
PA
Shamsuddin
Abulkalam
A
Rus
Horea
H
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
D018797:Cell Cycle Proteins; D006657:Histones; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C115049:RGCC protein, human