Response Gene to Complement 32 regulates chromatin assembly in colon cancer (100.35)

Abstract Response Gene to Complement 32 (RGC-32) is induced by complement activation and plays an important role in cell cycle activation. In this study we investigated the role of RGC-32 in colon cancer cell cycle. Our data indicate that RGC-32 expression is significantly higher in adenomas than in normal colon tissue. The expression of RGC-32 was higher in advanced stages than in precancerous states or the initial stages of colon cancer. In addition C5b-9 neoantigens deposits were found to be present on the colon tumor cells expressing RGC-32. In order to identify the genes that are regulated by RGC-32, we used gene array to investigate the effect of RGC-32 knockdown on gene expression in the SW480 cell line. Of the 230 genes that were differentially modulated by RGC-32, a group of genes involved in chromatin assembly were the most significantly regulated. RGC-32 knockdown induced an increase in acetylation of histones H2B lysine 5 (H2BK5), H2BK15, H3K9, H3K18, and H4K8, a decreased expression of SIRT1 and trimethylation of histone H3K27. In addition, RGC-32 knockdown caused a significantly higher percentage of SW480 cells to enter S phase, and subsequently G2/M. These results strongly suggest that silencing of the RGC-32 is associated with chromatin remodeling and activation of cell cycle. Since RGC-32 is induced by C5b-9 is possible that activation of complement has a benefic effect in colon cancer by inducing the expression of this tumor suppressor gene.