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

Interleukin-1 receptor antagonist (IL1RA) is an anti-inflammatory and anti-tumor protein, and a member of the Interleukin-1 (IL-1) family. Our previous finding showed that IL1RA is a tumor marker for oral squamous cell carcinoma (OSCC), but the exact mechanism is unknown. The present study aims to i...

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Main Authors: Yujie Ding, Yufei Shan, Jiaqi Gu, Jie Yi, Zhida Sun
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523325001597
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author Yujie Ding
Yufei Shan
Jiaqi Gu
Jie Yi
Zhida Sun
author_facet Yujie Ding
Yufei Shan
Jiaqi Gu
Jie Yi
Zhida Sun
author_sort Yujie Ding
collection DOAJ
description Interleukin-1 receptor antagonist (IL1RA) is an anti-inflammatory and anti-tumor protein, and a member of the Interleukin-1 (IL-1) family. Our previous finding showed that IL1RA is a tumor marker for oral squamous cell carcinoma (OSCC), but the exact mechanism is unknown. The present study aims to investigate the biological role of IL1RA in the progression of OSCC in vitro and in vivo and the underlying molecular mechanism. IL1RA was lowly expressed in OSCC specimens and cells, and its overexpression significantly inhibited the proliferation and migration of OSCC cell lines CAL27 and HN6. In nude mice bearing OSCC xenografts, in vivo overexpression of IL1RA significantly reduced tumor growth without influencing epithelial-mesenchymal transition (EMT). Differentially expressed genes (DEGs) in OSCC cells overexpressing IL1RA were identified by RNA sequencing (RNA-seq), and they were significantly enriched in cancer-associated signaling pathways like type I interferon response. IL1RA upregulated interferon alpha (IFNA) and interferon beta (IFNB), known for their anti-cancer properties, in OSCC cells and specimens. In conclusion, IL1RA inhibits the malignant progression of OSCC by mediating the type I interferon response.
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series Translational Oncology
spelling doaj-art-e5be1128d2a44a95b96557e7593764bf2025-08-20T03:20:55ZengElsevierTranslational Oncology1936-52332025-08-015810242810.1016/j.tranon.2025.102428IL1RA inhibits the progression of oral squamous cell carcinoma by mediating type Ⅰ interferon responseYujie Ding0Yufei Shan1Jiaqi Gu2Jie Yi3Zhida Sun4Department 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, ChinaDepartment 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, ChinaDepartment 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, ChinaYancheng Stomatological Hospital, Yancheng, Jiangsu, ChinaDepartment 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; Corresponding author at: Department of Endodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu 210029, China.Interleukin-1 receptor antagonist (IL1RA) is an anti-inflammatory and anti-tumor protein, and a member of the Interleukin-1 (IL-1) family. Our previous finding showed that IL1RA is a tumor marker for oral squamous cell carcinoma (OSCC), but the exact mechanism is unknown. The present study aims to investigate the biological role of IL1RA in the progression of OSCC in vitro and in vivo and the underlying molecular mechanism. IL1RA was lowly expressed in OSCC specimens and cells, and its overexpression significantly inhibited the proliferation and migration of OSCC cell lines CAL27 and HN6. In nude mice bearing OSCC xenografts, in vivo overexpression of IL1RA significantly reduced tumor growth without influencing epithelial-mesenchymal transition (EMT). Differentially expressed genes (DEGs) in OSCC cells overexpressing IL1RA were identified by RNA sequencing (RNA-seq), and they were significantly enriched in cancer-associated signaling pathways like type I interferon response. IL1RA upregulated interferon alpha (IFNA) and interferon beta (IFNB), known for their anti-cancer properties, in OSCC cells and specimens. In conclusion, IL1RA inhibits the malignant progression of OSCC by mediating the type I interferon response.http://www.sciencedirect.com/science/article/pii/S1936523325001597Oral squamous cell carcinomaInterleukin-1 receptor antagonistType I interferon responseInterferon αInterferon β
spellingShingle Yujie Ding
Yufei Shan
Jiaqi Gu
Jie Yi
Zhida Sun
IL1RA inhibits the progression of oral squamous cell carcinoma by mediating type Ⅰ interferon response
Translational Oncology
Oral squamous cell carcinoma
Interleukin-1 receptor antagonist
Type I interferon response
Interferon α
Interferon β
title IL1RA inhibits the progression of oral squamous cell carcinoma by mediating type Ⅰ interferon response
title_full IL1RA inhibits the progression of oral squamous cell carcinoma by mediating type Ⅰ interferon response
title_fullStr IL1RA inhibits the progression of oral squamous cell carcinoma by mediating type Ⅰ interferon response
title_full_unstemmed IL1RA inhibits the progression of oral squamous cell carcinoma by mediating type Ⅰ interferon response
title_short IL1RA inhibits the progression of oral squamous cell carcinoma by mediating type Ⅰ interferon response
title_sort il1ra inhibits the progression of oral squamous cell carcinoma by mediating type i interferon response
topic Oral squamous cell carcinoma
Interleukin-1 receptor antagonist
Type I interferon response
Interferon α
Interferon β
url http://www.sciencedirect.com/science/article/pii/S1936523325001597
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