CAPG interference induces apoptosis and ferroptosis in colorectal cancer cells through the P53 pathway

Mol Cell Probes. 2023 Oct:71:101919. doi: 10.1016/j.mcp.2023.101919. Epub 2023 Jul 30.

Abstract

Purpose: Given the high incidence and mortality rates of colorectal cancer (CRC) and the inadequacy of existing treatments for many patients, this study aimed to explore the potential of Capping Actin Protein (CAPG), a protein involved in actin-related movements, as a novel therapeutic target for CRC.

Methods: Bioinformatic analysis of gene expression was conducted using the UALCAN website. Cell proliferation was measured using the CCK-8 kit. Cell cycle, apoptosis, and ferroptosis were analyzed using flow cytometry. Tumorigenesis was evaluated by the subcutaneous inoculation of CRC cells into BALB/c nude female mice. Differentially expressed genes and signaling pathways were identified using RNA sequencing.

Results: CAPG was significantly overexpressed in human CRC tissues and its upregulation was correlated with poor overall survival. CAPG knockdown led to notable inhibition of CRC cells in vitro and in vivo. Interference with CAPG blocked the cell cycle at the G1 phase and triggered apoptosis and ferroptosis by upregulating the P53 pathway in CRC cells.

Conclusion: CRC patients with higher CAPG levels have a poorer prognosis. CAPG inhibits apoptosis and ferroptosis, while promoting CRC cell proliferation by repressing the P53 pathway. Our study suggests that CAPG may be a potential therapeutic target for CRC prognosis and treatment.

Keywords: Apoptosis; CAPG; CRC; Ferroptosis; P53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Female
  • Ferroptosis* / genetics
  • Humans
  • Mice
  • Microfilament Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Actins
  • CAPG protein, human
  • Microfilament Proteins
  • Nuclear Proteins
  • Tumor Suppressor Protein p53
  • TP53 protein, human