ART1 knockdown decreases IL-6-induced proliferation activity in colorectal cancer cells

Abstract Colorectal cancer (CRC) is a worldwide health concern. Chronic inflammation is a risk factor for CRC and IL-6 plays a central role in this process. Arginine-specific mono-ADP-ribosyltransferases-1 (ART1) is a positive regulator of inflammatory cytokines, and ART1 knockdown can reduce the transcriptional activation of the gene promoter of the signal transducer, glycoprotein (gp)130, in IL-6 signaling pathway. However, the relationship between ART1 and IL-6 and its effects on IL-6-induced proliferation in CRC remains unknown. Thus, the present study aimed to investigate the effects of ART1 knockdown on IL-6-induced cell proliferation in vitro, and used an in vivo murine model to observe the growth of the transplanted tumor. The results demonstrated that cancer cells transfected with ART1-sh exhibited lower viability, colony formation rate, DNA synthesis ability and protein expression levels of gp130, c-Myc, cyclin D1, Bcl-xL and phosphorylation ratio of p-STAT3/STAT3 (P < 0.05) after induction by IL-6. Moreover, the transplanted tumor volume of ART1-sh CT26 cells in mice with high IL-6 level was smaller (P < 0.05). It was also found that ART1 and gp130 had a co-localization relationship in CT26, LoVo and HCT116 cells, and there was a positive correlation between them in human CRC tissues. Taken together, ART1 may represent a novel and effective regulatory factor for IL-6 signaling and that it may serve as a new therapeutic target for human CRC.