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Peer-reviewedCC BY-NC-NDJournal of biochemical and molecular toxicology

XDH Inhibits the Progression of Colorectal Cancer via Regulating Ferritinophagy Signaling.

  • Huiying Zhang1
  • Meimei Yan1
  • Mengya Li2
  • Junjiao Gu3
  • Xintao Wang4
  • Jin Ding2
  • Suxia Luo1
4 affiliations
  1. 1Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China.
  2. 2Department of Oncology, The First Affiliated Hospital of Henan University, Kaifeng, Henan, China.
  3. 3Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, Henan, China.
  4. 4Department of General surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan, China.
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Abstract

Xanthine dehydrogenase (XDH) is involved in the progression of various cancer. This study aimed to investigate its potential in colorectal cancer (CRC). Gene expression was determined using RT-qPCR, Western blot, immunohistochemistry, and immunofluorescence. Cell behaviors were analyzed using CCK-8, colony formation, wound healing, transwell migration, TUNEL, PI staining. In vivo assay was conducted to verify the role of XDH in CRC. Histological analysis was performed using HE staining. We found that XDH was downregulated in CRC. XDH overexpression suppressed proliferation and aggressiveness of CRC cells, whereas XDH knockdown exerted opposite effects. XDH selectively increased purine metabolites and promoted impairment of mitochondrial metabolism. Mechanistically, XDH activated NCOA4-dependent ferritinophagy signaling and drove CRC cells to ferroptosis, which was reversed by 3-MA. Taken together, XDH inhibits the progression of CRC via mediating ferritinophagy and ferroptosis. Therefore, XDH/ferritinophagy may be a potential target for CRC.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026inhibits,
  title = {{XDH Inhibits the Progression of Colorectal Cancer via Regulating Ferritinophagy Signaling.}},
  author = {Huiying Zhang and Meimei Yan and Mengya Li and Junjiao Gu and Xintao Wang and Jin Ding and Suxia Luo},
  journal = {Journal of biochemical and molecular toxicology},
  year = {2026},
  month = oct,
  doi = {10.1002/jbt.71145},
  url = {https://europepmc.org/article/MED/42927618},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - XDH Inhibits the Progression of Colorectal Cancer via Regulating Ferritinophagy Signaling.
AU  - Huiying Zhang
AU  - Meimei Yan
AU  - Mengya Li
AU  - Junjiao Gu
AU  - Xintao Wang
AU  - Jin Ding
AU  - Suxia Luo
PY  - 2026
DA  - 2026/10/30
JO  - Journal of biochemical and molecular toxicology
DO  - 10.1002/jbt.71145
UR  - https://europepmc.org/article/MED/42927618
AB  - Xanthine dehydrogenase (XDH) is involved in the progression of various cancer. This study aimed to investigate its potential in colorectal cancer (CRC). Gene expression was determined using RT-qPCR, Western blot, immunohistochemistry, and immunofluorescence. Cell behaviors were analyzed using CCK-8, colony formation, wound healing, transwell migration, TUNEL, PI staining. In vivo assay was conducted to verify the role of XDH in CRC. Histological analysis was performed using HE staining. We found that XDH was downregulated in CRC. XDH overexpression suppressed proliferation and aggressiveness of CRC cells, whereas XDH knockdown exerted opposite effects. XDH selectively increased purine metabolites and promoted impairment of mitochondrial metabolism. Mechanistically, XDH activated NCOA4-dependent ferritinophagy signaling and drove CRC cells to ferroptosis, which was reversed by 3-MA. Taken together, XDH inhibits the progression of CRC via mediating ferritinophagy and ferroptosis. Therefore, XDH/ferritinophagy may be a potential target for CRC.
SN  - 1095-6670
SN  - 1099-0461
ER  -