2. Academic Validation
  3. The m6A modification reader protein IGF2BP2 regulates ferroptosis in nasopharyngeal carcinoma cells by stabilizing CP expression via an m6A-dependent mechanism

The m6A modification reader protein IGF2BP2 regulates ferroptosis in nasopharyngeal carcinoma cells by stabilizing CP expression via an m6A-dependent mechanism

  • Biochem Biophys Res Commun. 2025 Sep 8:778:152417. doi: 10.1016/j.bbrc.2025.152417.
Yanyan Yuan 1,  Yuanzhao Lan 2,  Jia Li 3,  Yi Cui 4,  Juan Zhou 5,  Haojie Wen 6
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology Head and Neck Surgery, The First People's Hospital of Chenzhou, Chenzhou, 423000, China. Electronic address: 19193863@qq.com.
  • 2 Department of Otorhinolaryngology Head and Neck Surgery, The First People's Hospital of Chenzhou, Chenzhou, 423000, China. Electronic address: 793242698@qq.com.
  • 3 The First People's Hospital of Chenzhou, First Clinical College of Xiangnan University, The First Affiliated Hospital of Xiangnan University, Chenzhou, 423000, China; Translational Medicine Institute, The First People's Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, 423000, China. Electronic address: 280524653@qq.com.
  • 4 Department of Otorhinolaryngology Head and Neck Surgery, The First People's Hospital of Chenzhou, Chenzhou, 423000, China. Electronic address: sanlongtree@163.com.
  • 5 Department of Otorhinolaryngology Head and Neck Surgery, The First People's Hospital of Chenzhou, Chenzhou, 423000, China. Electronic address: 1075765033@qq.com.
  • 6 Department of Otorhinolaryngology Head and Neck Surgery, The First People's Hospital of Chenzhou, Chenzhou, 423000, China; Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Xiangnan University, Chenzhou, 423000, China. Electronic address: wenhaojie1886@163.com.
PMID: 40743989 DOI: 10.1016/j.bbrc.2025.152417
Abstract

In this study, we explored the role of IGF2BP2 in nasopharyngeal carcinoma (NPC) and its link to Ferroptosis, a form of regulated cell death associated with Cancer progression. Through bioinformatics analysis of the GSE53819 dataset, we identified differentially expressed genes, performed survival analysis, and conducted pan-cancer studies, revealing that IGF2BP2 is overexpressed in NPC and associated with poor prognosis. Clinical sample analysis and cellular experiments confirmed IGF2BP2 upregulation in NPC and its ability to induce Ferroptosis when knocked down. We discovered five downstream factors of IGF2BP2 that are associated with Ferroptosis, comprising Ceruloplasmin (CP), SLC7A11, SLC40A1, STEAP3, and TFRC, with CP being notably correlated with the prognosis of patients with NPC. IGF2BP2 enhances CP mRNA stability through N6-methyladenosine (m6A) methylation, influencing Ferroptosis and proliferation in NPC cells. In nude mouse xenograft models, IGF2BP2 knockdown inhibited tumor growth and altered the expression of CP, GPX4, and Ferroptosis markers. Collectively, our findings suggest that IGF2BP2 may serve as a therapeutic target in NPC by modulating m6A modification and CP stability to inhibit Ferroptosis.

Keywords

CP; Ferroptosis; IGF2BP2; N6-methyladenosine; Nasopharyngeal carcinoma.

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