Iodine-125 seed induces ferroptosis through inhibiting RNF216-mediated ubiquitination of p53 in cholangiocarcinoma cells.

Authors

Jing Wu, Xiaoning Chang, Jianjun Song, Fuping Kang

Published in

Cytotechnology. Volume 78. Issue 4. Pages 147. Epub Jun 29, 2026.

Abstract

Iodine-125 (¹²⁵I) seed has effectively treated cholangiocarcinoma (CCA) in previous research. Ferroptosis, a new form of programmed cell death, is linked to cancers including CCA. However, the relationship between ¹²⁵I seed and ferroptosis in CCA requires further investigation. Five pairs of CCA and adjacent normal tissue were collected, CCA tissues then were subjected to ¹²⁵I seed brachytherapy. The optimal ¹²⁵I seed dose for irradiating RBE cells was determined using the CCK-8 assay, and the cells were treated with ferroptosis inhibitors or MG132. RNF216 expression was modulated by short interfering RNA (siRNA) or overexpression plasmid. Cell viability, proliferation, and apoptosis were evaluated by CCK-8, EdU assays, TUNEL staining, and flow cytometric analysis. Intracellular Fe²⁺ levels, Lipid reactive oxygen species (ROS) and the GSH/GSSG ratio were detected by an iron assay kit, C11-BODIPY 581/591 and the EZ-Glutathione Assay Kit, respectively. The expression of RNF216, p53, SLC7A11 and GPX4 were analyzed by RT-qPCR and Western Blot. Ubiquitination of p53 by RNF216 was verified through ubiquitination immunoprecipitation. In CCA cell and tissues, ¹²⁵I seed induced ferroptosis and reduced RNF216 expression. Additionally, ¹²⁵I seed inhibited cell viability and proliferation but promoted apoptosis, and these trends were reversed by RNF216 overexpression or ferroptosis inhibitors. RNF216 was a key regulator of ¹²⁵I seed-induced ferroptosis. Mechanistically, RNF216 promoted p53 degradation through ubiquitination, leading to upregulated SLC7A11 expression and ultimately inhibiting ferroptosis.¹²⁵I seed inhibited SLC7A11 expression by preventing RNF216-mediated ubiquitination of p53, ultimately inducing ferroptosis in CCA. This provides crucial molecular evidence for the anticancer effects of ¹²⁵I seed.

PMID:
42375926
Bibliographic data and abstract were imported from PubMed on 30 Jun 2026.

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