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Peer-reviewedCC BY-NC 4.0The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology

IRF4 transcriptionally activates CD36 to regulate glycolysis and suppress oxaliplatin resistance in colorectal cancer

  • Qing Sun1
  • Dongliang Zhao1
  • Zhongcai Yao2
  • Ruolin Sun3
  • Yefei Zhang4
4 affiliations
  1. 1Department of Gastroentero-anorectal Surgery, Zhuji Affiliated Hospital of Wenzhou Medical University, Shaoxing Zhejiang 311800 China
  2. 2Department of Infectious Diseases, Zhuji Affiliated Hospital of Wenzhou Medical University, Shaoxing Zhejiang 311800 China
  3. 3Hangzhou Medical College Hangzhou Zhejiang 310000 China
  4. 4Clinical Pharmaceutics Room, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, Shaoxing Zhejiang 311800 China
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Abstract

Oxaliplatin (OXA) resistance in colorectal cancer (CRC) remains a major therapeutic challenge, prompting investigation into the role of the interferon regulatory factor 4 (IRF4)/leukocyte differentiation antigen 36 (CD36) regulatory axis and its impact on glycolysis. Bioinformatic analysis identified CD36 as a key gene, with IRF4 predicted as its upstream regulator. OXA-resistant CRC cell lines were established. Gene expression was analyzed by reverse transcription quantitative polymerase chain reaction and Western blot. The IRF4-CD36 interaction was validated via chromatin immunoprecipitation and dual-luciferase assays. Glycolysis was assessed by measuring glucose consumption, lactate production, and ATP levels. Drug sensitivity was evaluated using cell counting kit-8 and apoptosis assays. Both IRF4 and CD36 were downregulated in OXA-resistant cells. IRF4 directly bound to the CD36 promoter to activate its transcription. Overexpression of CD36 or IRF4 inhibited glycolysis and restored OXA sensitivity. Knockdown of CD36 in IRF4-overexpressing cells reversed these effects, confirming CD36 as the functional mediator. The study demonstrates that the IRF4/CD36 axis attenuates OXA resistance in CRC by transcriptional repression of glycolysis. This axis presents a promising therapeutic target for overcoming chemoresistance.

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Cite

BibTeXRIS
BibTeX
@article{sun2026irf4,
  title = {{IRF4 transcriptionally activates CD36 to regulate glycolysis and suppress oxaliplatin resistance in colorectal cancer}},
  author = {Qing Sun and Dongliang Zhao and Zhongcai Yao and Ruolin Sun and Yefei Zhang},
  journal = {The Korean Journal of Physiology \& Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology},
  year = {2026},
  month = nov,
  doi = {10.4196/kjpp.25.448},
  url = {https://doi.org/10.4196/kjpp.25.448},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - IRF4 transcriptionally activates CD36 to regulate glycolysis and suppress oxaliplatin resistance in colorectal cancer
AU  - Qing Sun
AU  - Dongliang Zhao
AU  - Zhongcai Yao
AU  - Ruolin Sun
AU  - Yefei Zhang
PY  - 2026
DA  - 2026/11/01
JO  - The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
DO  - 10.4196/kjpp.25.448
UR  - https://doi.org/10.4196/kjpp.25.448
AB  - Oxaliplatin (OXA) resistance in colorectal cancer (CRC) remains a major therapeutic challenge, prompting investigation into the role of the interferon regulatory factor 4 (IRF4)/leukocyte differentiation antigen 36 (CD36) regulatory axis and its impact on glycolysis. Bioinformatic analysis identified CD36 as a key gene, with IRF4 predicted as its upstream regulator. OXA-resistant CRC cell lines were established. Gene expression was analyzed by reverse transcription quantitative polymerase chain reaction and Western blot. The IRF4-CD36 interaction was validated via chromatin immunoprecipitation and dual-luciferase assays. Glycolysis was assessed by measuring glucose consumption, lactate production, and ATP levels. Drug sensitivity was evaluated using cell counting kit-8 and apoptosis assays. Both IRF4 and CD36 were downregulated in OXA-resistant cells. IRF4 directly bound to the CD36 promoter to activate its transcription. Overexpression of CD36 or IRF4 inhibited glycolysis and restored OXA sensitivity. Knockdown of CD36 in IRF4-overexpressing cells reversed these effects, confirming CD36 as the functional mediator. The study demonstrates that the IRF4/CD36 axis attenuates OXA resistance in CRC by transcriptional repression of glycolysis. This axis presents a promising therapeutic target for overcoming chemoresistance.
SN  - 1226-4512
SN  - 2093-3827
ER  -