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IL1RA inhibits the progression of oral squamous cell carcinoma by mediating type Ⅰ interferon response

Yujie Ding1, Yufei Shan1, Jiaqi Gu1

  • 1Department of Endodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing, Jiangsu, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, Jiangsu, China.

Translational Oncology
|May 29, 2025
PubMed

Insights

Interleukin-1 receptor antagonist (IL1RA) acts as an anti-tumor protein in oral squamous cell carcinoma (OSCC). Overexpressing IL1RA inhibits OSCC progression by activating the type I interferon response, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Interleukin-1 receptor antagonist (IL1RA) is an anti-inflammatory and anti-tumor protein within the Interleukin-1 family.
  • Previous research identified IL1RA as a tumor marker for oral squamous cell carcinoma (OSCC), but its precise mechanism of action remained unclear.

Purpose of the Study:

  • To elucidate the biological role of IL1RA in oral squamous cell carcinoma (OSCC) progression.
  • To investigate the underlying molecular mechanisms by which IL1RA influences OSCC development in vitro and in vivo.

Main Methods:

  • Overexpression of IL1RA in OSCC cell lines (CAL27, HN6) and in vivo xenograft models.
  • Assessment of cell proliferation, migration, and tumor growth.
  • RNA sequencing (RNA-seq) to identify differentially expressed genes (DEGs).
  • Analysis of signaling pathways, including type I interferon response, and expression of interferon alpha (IFNA) and interferon beta (IFNB).

Main Results:

  • IL1RA was found to be lowly expressed in OSCC specimens and cells.
  • Overexpression of IL1RA significantly inhibited OSCC cell proliferation and migration.
  • In vivo, IL1RA overexpression reduced tumor growth in nude mice without affecting epithelial-mesenchymal transition (EMT).
  • RNA-seq revealed enrichment of cancer-associated pathways, particularly the type I interferon response, in IL1RA-overexpressing OSCC cells.
  • IL1RA upregulated the expression of IFNA and IFNB in OSCC cells and specimens.

Conclusions:

  • IL1RA demonstrates significant anti-tumor effects in oral squamous cell carcinoma (OSCC).
  • The anti-cancer properties of IL1RA are mediated through the upregulation of the type I interferon response.
  • IL1RA holds potential as a therapeutic agent for inhibiting OSCC malignant progression.
Keywords:
Interferon αInterferon βInterleukin-1 receptor antagonistOral squamous cell carcinomaType I interferon response

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