2. Academic Validation
  3. ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells

ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells

  • BMC Cancer. 2024 Mar 19;24(1):354. doi: 10.1186/s12885-024-12120-0.
Ting Lin # 1,  Shuxian Zhang # 1 2,  Yi Tang 1 3,  Ming Xiao 1 2,  Ming Li 1 3,  Hanjuan Gong 1,  Hailun Xie 1,  Yalan Wang 4 5 6
Affiliations

Affiliations

  • 1 Department of Pathology, Molecular Medicine and Cancer Research Center, Basic Medicine College, Chongqing Medical University, Chongqing, 400016, P.R. China.
  • 2 Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, 400016, P.R. China.
  • 3 Department of Pathology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China.
  • 4 Department of Pathology, Molecular Medicine and Cancer Research Center, Basic Medicine College, Chongqing Medical University, Chongqing, 400016, P.R. China. wangyalan@cqmu.edu.cn.
  • 5 Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, 400016, P.R. China. wangyalan@cqmu.edu.cn.
  • 6 Department of Pathology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China. wangyalan@cqmu.edu.cn.
  • # Contributed equally.
PMID: 38504172 DOI: 10.1186/s12885-024-12120-0
Abstract

Colorectal Cancer (CRC) is a worldwide health concern. Chronic inflammation is a risk factor for CRC, and interleukin-6 (IL-6) plays a pivotal role in this process. Arginine-specific mono-ADP-ribosyltransferase-1 (ART1) positively regulates inflammatory cytokines. ART1 knockdown reduces the level of glycoprotein 130 (gp130), a key transducer in the IL-6 signalling pathway. However, the relationship between ART1 and IL-6 and the resulting effects on IL-6-induced proliferation in CRC cells remain unclear. The aims of this study were to investigate the effects of ART1 knockdown on IL-6-induced cell proliferation in vitro and use an in vivo murine model to observe the growth of transplanted tumours. The results showed that compared with the control, ART1-sh Cancer cells induced by IL-6 exhibited reduced viability, a lower rate of colony formation, less DNA synthesis, decreased protein levels of gp130, c-Myc, cyclin D1, Bcl-xL, and a reduced p-STAT3/STAT3 ratio (P < 0.05). Moreover, mice transplanted with ART1-sh CT26 cells that had high levels of IL-6 displayed tumours with smaller volumes (P < 0.05). ART1 and gp130 were colocalized in CT26, LoVo and HCT116 cells, and their expression was positively correlated in human CRC tissues. Overall, ART1 may serve as a promising regulatory factor for IL-6 signalling and a potential therapeutic target for human CRC.

Keywords

ART1; Cell proliferation; Colorectal cancer; IL-6; gp130.

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