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High‑dose sodium propionate contributes to tumor immune escape through the IGF2BP3/PD‑L1 axis in colorectal cancer

  • Authors:
    • Xun Wang
    • Yikui Hu
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Wuhan Wuchang Hospital, Wuchang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430063, P.R. China, Department of Neurology, Wuhan Wuchang Hospital, Wuchang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430063, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 303
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    Published online on: April 16, 2025
       https://doi.org/10.3892/ol.2025.15049
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Abstract

The understanding of how gut microbiota metabolites modulate immune escape mechanisms in colorectal cancer (CRC) remains limited. In the present study, the impact of gut microbiota metabolites on the efficacy of programmed cell death protein 1 (PD‑1) and programmed cell death ligand‑1 (PD‑L1) immunotherapy in CRC was explored, with a particular focus on the short‑chain fatty acid, sodium propionate (SP), as they key metabolite. The results of the present study, determined by CCK‑8 and flow cytometry, demonstrated that 10 mM SP significantly suppressed CRC cell proliferation and induced apoptosis. By contrast, 40 mM SP, but not 10 mM, markedly increased the PD‑L1 mRNA and protein expression levels. Insulin‑like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression, analyzed via bioinformatics using The Cancer Genoma Atlas datasets, was significantly higher in CRC tissues compared with healthy tissues. Additionally, survival analysis uncovered that elevated IGF2BP3 levels in tumor tissues were strongly associated with poor clinical outcomes. Moreover, 40 mM SP significantly induced the expression of IGF2BP3 mRNA and protein in CRC cells. The actinomycin D assay was conducted to assess mRNA stability, whereas methylated RNA immunoprecipitation coupled with quantitative polymerase chain reaction (qPCR) and RNA immunoprecipitation‑qPCR were utilized to confirm the interaction between IGF2BP3 and PD‑L1 mRNA. These results indicated that IGF2BP3 served as an N6‑methyladenosine (m6A) reader for PD‑L1, stabilizing its mRNA in an m6A‑dependent manner, thereby upregulating the PD‑L1 mRNA and protein expression levels. Therefore, high‑dose SP may promote tumor immune escape via the IGF2BP3/PD‑L1 axis in CRC. As such, high‑dose SP may synergize with PD‑1/PD‑L1 blockade therapies to improve clinical outcomes in patients with CRC, particularly by upregulating PD‑L1 expression.
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Copy and paste a formatted citation
Spandidos Publications style
Wang X and Hu Y: High‑dose sodium propionate contributes to tumor immune escape through the IGF2BP3/PD‑L1 axis in colorectal cancer. Oncol Lett 29: 303, 2025.
APA
Wang, X., & Hu, Y. (2025). High‑dose sodium propionate contributes to tumor immune escape through the IGF2BP3/PD‑L1 axis in colorectal cancer. Oncology Letters, 29, 303. https://doi.org/10.3892/ol.2025.15049
MLA
Wang, X., Hu, Y."High‑dose sodium propionate contributes to tumor immune escape through the IGF2BP3/PD‑L1 axis in colorectal cancer". Oncology Letters 29.6 (2025): 303.
Chicago
Wang, X., Hu, Y."High‑dose sodium propionate contributes to tumor immune escape through the IGF2BP3/PD‑L1 axis in colorectal cancer". Oncology Letters 29, no. 6 (2025): 303. https://doi.org/10.3892/ol.2025.15049
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X and Hu Y: High‑dose sodium propionate contributes to tumor immune escape through the IGF2BP3/PD‑L1 axis in colorectal cancer. Oncol Lett 29: 303, 2025.
APA
Wang, X., & Hu, Y. (2025). High‑dose sodium propionate contributes to tumor immune escape through the IGF2BP3/PD‑L1 axis in colorectal cancer. Oncology Letters, 29, 303. https://doi.org/10.3892/ol.2025.15049
MLA
Wang, X., Hu, Y."High‑dose sodium propionate contributes to tumor immune escape through the IGF2BP3/PD‑L1 axis in colorectal cancer". Oncology Letters 29.6 (2025): 303.
Chicago
Wang, X., Hu, Y."High‑dose sodium propionate contributes to tumor immune escape through the IGF2BP3/PD‑L1 axis in colorectal cancer". Oncology Letters 29, no. 6 (2025): 303. https://doi.org/10.3892/ol.2025.15049
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