CircCCT2/miR-146a-5p/IRAK1 axis promotes the development of head and neck squamous cell carcinoma

Long He^{1 2}, Lanruo Li³, Liting Zhao^{4 5}, Xiaoya Guan^{4 5}, Yujia Guo^{4 5}, Qi Han^{4 5}, Huina Guo^{6 7}, Hongliang Liu^{8 9 10 11}, Chunming Zhang^{12 13 14}

Affiliations

¹ Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. hl@sxent.org.
² Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. hl@sxent.org.
³ The First Clinical Medical College of Shanxi Medical University, Taiyuan, 030001, China.
⁴ Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China.
⁵ Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China.
⁶ Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. guohuina@sxent.org.
⁷ Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. guohuina@sxent.org.
⁸ Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. liuhl2018@sxent.org.
⁹ Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. liuhl2018@sxent.org.
¹⁰ Department of Otolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. liuhl2018@sxent.org.
¹¹ Departments of Cell Biology and Genetics, the Basic Medical School of Shanxi Medical University, Taiyuan, 030001, Shanxi, China. liuhl2018@sxent.org.
¹² Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. zcmsxmu@sxent.org.
¹³ Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. zcmsxmu@sxent.org.
¹⁴ Department of Otolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. zcmsxmu@sxent.org.

PMID: 39810134
PMCID: PMC11734332
DOI: 10.1186/s12885-025-13464-x

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.

Keywords: EMT; Head and neck squamous cell carcinoma; IRAK1; circCCT2; miR-146a-5p.

BMC Cancer. 2025 Jan 14;25(1):84.doi: 10.1186/s12885-025-13464-x.

CircCCT2/miR-146a-5p/IRAK1 axis promotes the development of head and neck squamous cell carcinoma

Abstract

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