2. Academic Validation
  3. CLIC1 regulates cellular oxidative stress and gastric cancer progress by enhancing ACOX1 ubiquitination

CLIC1 regulates cellular oxidative stress and gastric cancer progress by enhancing ACOX1 ubiquitination

  • Int J Biol Macromol. 2025 Oct 13;330(Pt 4):148292. doi: 10.1016/j.ijbiomac.2025.148292.
Changhua Li 1,  Jian Yang 2,  Weijia Huang 2,  Shengyu Wang 3,  Yue Feng 2,  Tiande Chen 2,  Wenqian Xu 2,  Junqiang Chen 4
Affiliations

Affiliations

  • 1 Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, China; Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, China.
  • 2 Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, China; Guangxi Clinical Research Center for Enhanced Recovery after Surgery, Nanning, China.
  • 3 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China; Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, China; Guangxi Clinical Research Center for Enhanced Recovery after Surgery, Nanning, China.
  • 4 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China; Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, China; Guangxi Clinical Research Center for Enhanced Recovery after Surgery, Nanning, China. Electronic address: chenjunqiang@gxmu.edu.cn.
PMID: 41093222 DOI: 10.1016/j.ijbiomac.2025.148292
Abstract

Oxidative stress is a two-edged sword for tumors. However, how oxidative stress influences tumor progression remains unclear. We determined that chloride intracellular channel 1 (CLIC1) accelerates gastric Cancer progression by enhancing acyl-CoA oxidase 1 (ACOX1) ubiquitination and increasing cellular oxidative stress. CLIC1 overexpression increased cellular oxidative stress. Furthermore, our results demonstrate that ACOX1 is an oxidative stress-related gene that is closely related to CLIC1. Functionally, downregulating ACOX1 promoted gastric Cancer cell proliferation, migration, and invasion. Mechanistically, the CLIC1 protein bound to the ACOX1 protein, reducing its protein stability and facilitating polyubiquitination-dependent proteasomal degradation. The consequent loss of ACOX1 enhances cellular oxidative stress, which promotes gastric Cancer progression. Furthermore, ACOX1 was significantly downregulated in gastric Cancer, indicating a poor clinical prognosis. Our results elucidates the key pathway through which high CLIC1 expression enhances cellular oxidative stress, subsequently promoting gastric Cancer progression. Therefore, CLIC1 might function as a redox regulation therapy target and a tumor marker.

Keywords

ACOX1; CLIC1; Gastric cancer progression; Oxidative stress; Ubiquitination.

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