CircCCT2/miR-146a-5p/IRAK1 axis promotes the development of head and neck squamous cell carcinoma
Abstract Background Head and neck squamous cell carcinoma (HNSCC), a highly invasive malignancy with a poor prognosis, is one of the most common cancers globally. Circular RNAs (circRNAs) have become key regulators of human malignancies, but further studies are necessary to fully understand their fu...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12885-025-13464-x |
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| author | Long He Lanruo Li Liting Zhao Xiaoya Guan Yujia Guo Qi Han Huina Guo Hongliang Liu Chunming Zhang |
| author_facet | Long He Lanruo Li Liting Zhao Xiaoya Guan Yujia Guo Qi Han Huina Guo Hongliang Liu Chunming Zhang |
| author_sort | Long He |
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| description | Abstract Background Head and neck squamous cell carcinoma (HNSCC), a highly invasive malignancy with a poor prognosis, is one of the most common cancers globally. Circular RNAs (circRNAs) have become key regulators of human malignancies, but further studies are necessary to fully understand their functions and possible causes in HNSCC. Methods CircCCT2 expression levels in HNSCC tissues and cells were measured via qPCR. CircCCT2 was characterized by Sanger sequencing, qRT-PCR, RNase R & Actinomycin D treatment, nucleoplasmic separation and FISH experiments. CCK-8 and colony formation assays were performed to determine cell proliferation, and Transwell assays were used to determine migration and invasion. A xenograft tumor model was used to study the influence of circCCT2 on HNSCC in vivo. Dual-luciferase gene reporter, RIP, western blotting, and rescue experiments, were used to explore target-binding relationships and regulatory mechanisms. Results CircCCT2 was significantly upregulated in HNSCC tissues and cells. High circCCT2 levels were associated with advanced T stage, N stage, clinical stage and poor prognosis. Functionally, we verified that circCCT2 promotes HNSCC development in vitro and in vivo. Mechanistically, functioning as a competitive endogenous RNA (ceRNA) or miRNA sponge, circCCT2 binds directly to miR-146a-5p and increases interleukin-1 receptor-associated kinase 1 (IRAK1) levels, which enhances the malignant development of HNSCC by driving epithelial-mesenchymal transition (EMT). Conclusion CircCCT2 promotes HNSCC development through the miR-146a-5p/IRAK1 axis, revealing that circCCT2 is a potential biomarker and target for HNSCC. |
| format | Article |
| id | doaj-art-b97b2fdfae654a57a6c532c3b2efbd34 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-b97b2fdfae654a57a6c532c3b2efbd342025-01-19T12:26:52ZengBMCBMC Cancer1471-24072025-01-0125111710.1186/s12885-025-13464-xCircCCT2/miR-146a-5p/IRAK1 axis promotes the development of head and neck squamous cell carcinomaLong He0Lanruo Li1Liting Zhao2Xiaoya Guan3Yujia Guo4Qi Han5Huina Guo6Hongliang Liu7Chunming Zhang8Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical UniversityThe First Clinical Medical College of Shanxi Medical UniversityShanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical UniversityShanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical UniversityShanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical UniversityShanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical UniversityShanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical UniversityShanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical UniversityShanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical UniversityAbstract Background Head and neck squamous cell carcinoma (HNSCC), a highly invasive malignancy with a poor prognosis, is one of the most common cancers globally. Circular RNAs (circRNAs) have become key regulators of human malignancies, but further studies are necessary to fully understand their functions and possible causes in HNSCC. Methods CircCCT2 expression levels in HNSCC tissues and cells were measured via qPCR. CircCCT2 was characterized by Sanger sequencing, qRT-PCR, RNase R & Actinomycin D treatment, nucleoplasmic separation and FISH experiments. CCK-8 and colony formation assays were performed to determine cell proliferation, and Transwell assays were used to determine migration and invasion. A xenograft tumor model was used to study the influence of circCCT2 on HNSCC in vivo. Dual-luciferase gene reporter, RIP, western blotting, and rescue experiments, were used to explore target-binding relationships and regulatory mechanisms. Results CircCCT2 was significantly upregulated in HNSCC tissues and cells. High circCCT2 levels were associated with advanced T stage, N stage, clinical stage and poor prognosis. Functionally, we verified that circCCT2 promotes HNSCC development in vitro and in vivo. Mechanistically, functioning as a competitive endogenous RNA (ceRNA) or miRNA sponge, circCCT2 binds directly to miR-146a-5p and increases interleukin-1 receptor-associated kinase 1 (IRAK1) levels, which enhances the malignant development of HNSCC by driving epithelial-mesenchymal transition (EMT). Conclusion CircCCT2 promotes HNSCC development through the miR-146a-5p/IRAK1 axis, revealing that circCCT2 is a potential biomarker and target for HNSCC.https://doi.org/10.1186/s12885-025-13464-xHead and neck squamous cell carcinomacircCCT2miR-146a-5pIRAK1EMT |
| spellingShingle | Long He Lanruo Li Liting Zhao Xiaoya Guan Yujia Guo Qi Han Huina Guo Hongliang Liu Chunming Zhang CircCCT2/miR-146a-5p/IRAK1 axis promotes the development of head and neck squamous cell carcinoma BMC Cancer Head and neck squamous cell carcinoma circCCT2 miR-146a-5p IRAK1 EMT |
| title | CircCCT2/miR-146a-5p/IRAK1 axis promotes the development of head and neck squamous cell carcinoma |
| title_full | CircCCT2/miR-146a-5p/IRAK1 axis promotes the development of head and neck squamous cell carcinoma |
| title_fullStr | CircCCT2/miR-146a-5p/IRAK1 axis promotes the development of head and neck squamous cell carcinoma |
| title_full_unstemmed | CircCCT2/miR-146a-5p/IRAK1 axis promotes the development of head and neck squamous cell carcinoma |
| title_short | CircCCT2/miR-146a-5p/IRAK1 axis promotes the development of head and neck squamous cell carcinoma |
| title_sort | circcct2 mir 146a 5p irak1 axis promotes the development of head and neck squamous cell carcinoma |
| topic | Head and neck squamous cell carcinoma circCCT2 miR-146a-5p IRAK1 EMT |
| url | https://doi.org/10.1186/s12885-025-13464-x |
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