2. Academic Validation
  3. Upregulated ARMCX1 suppresses nasopharyngeal carcinoma progression by promoting TRIM21-mediated β-catenin degradation

Upregulated ARMCX1 suppresses nasopharyngeal carcinoma progression by promoting TRIM21-mediated β-catenin degradation

  • Cell Oncol (Dordr). 2026 Jan 14;49(1):25. doi: 10.1007/s13402-025-01161-7.
Zhe Hu # 1,  Enqing Zhuo # 2,  Jiankang Guo # 3,  Yilin Wu 4,  Xiaoou Sun 5,  Houkuang Qiu 6,  Yangfan Zhou 7,  Xi Tan 7,  Xuhui Zhang 8
Affiliations

Affiliations

  • 1 Department of Second Ward Oncology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China.
  • 2 Department of Second Ward Oncology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China. [email protected].
  • 3 Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, China.
  • 4 Department of Cardiology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China.
  • 5 Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China.
  • 6 Department of Laboratory Medicine, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China.
  • 7 Department of Pathology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China.
  • 8 Department of Second Ward Oncology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China. [email protected].
  • # Contributed equally.
PMID: 41533266 DOI: 10.1007/s13402-025-01161-7
Abstract

Background: Armadillo repeat-containing X-linked 1 (ARMCX1) has been reported to exhibit a suppressive effect in a variety of solid tumors. However, neither its biological role nor its potential mechanism of action has yet been reported in nasopharyngeal carcinoma (NPC).

Methods: Immunohistochemical staining of an NPC tissue microarray was performed to evaluate the clinicopathologic association between ARMCX1 and NPC patients. The effect of ARMCX1 on the growth, migratory, and invasive capacities of NPC cells was assessed in vitro using colony formation, Cell Counting Kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), scratch, and Transwell assays. A subcutaneous graft tumor model was implemented to investigate the impact of ARMCX1 on the tumor growth of NPC cells in vivo. Western blotting, immunofluorescence staining, and cycloheximide and Proteasome Inhibitor experiments were employed to investigate the potential molecular mechanisms of ARMCX1 in NPC

Results: Overexpression of ARMCX1 effectively inhibited the growth, migration, and invasion in NPC cells. Western blotting, co-immunoprecipitation, immunofluorescence, and cycloheximide and Proteasome Inhibitor experiments revealed that ARMCX1 mediated the β-catenin ubiquitination and degradation via recruiting tripartite motif-containing protein 21 (TRIM21), thereby suppressing cell cycle progression and epithelial–mesenchymal transition. Final rescue assays demonstrated that β-catenin reversed ARMCX1-mediated suppression of NPC cell proliferation, migration, and invasion.

Conclusions: ARMCX1 attenuates NPC cell proliferation, migration, and invasion by binding β-catenin and promoting its ubiquitination-dependent degradation via TRIM21. Hence, ARMCX1 may serve as a potential molecular target for therapeutic intervention in NPC.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13402-025-01161-7.

Keywords

ARMCX1; Nasopharyngeal carcinoma; TRIM21; Ubiquitination; β-catenin.

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