He Long, Li Lanruo, Zhao Liting, Guan Xiaoya, Guo Yujia, Han Qi, Guo Huina, Liu Hongliang, Zhang Chunming
Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China.
Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China.
BMC Cancer. 2025 Jan 14;25(1):84. doi: 10.1186/s12885-025-13464-x.
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.
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.
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).
CircCCT2 promotes HNSCC development through the miR-146a-5p/IRAK1 axis, revealing that circCCT2 is a potential biomarker and target for HNSCC.
头颈部鳞状细胞癌（HNSCC）是一种侵袭性很强且预后较差的恶性肿瘤，是全球最常见的癌症之一。环状RNA（circRNAs）已成为人类恶性肿瘤的关键调节因子，但需要进一步研究以全面了解其在HNSCC中的功能及可能的成因。
通过qPCR检测HNSCC组织和细胞中CircCCT2的表达水平。通过Sanger测序、qRT-PCR、RNase R和放线菌素D处理、核质分离及FISH实验对CircCCT2进行鉴定。进行CCK-8和集落形成实验以确定细胞增殖情况，并使用Transwell实验确定迁移和侵袭能力。采用异种移植肿瘤模型在体内研究CircCCT2对HNSCC的影响。使用双荧光素酶基因报告、RIP、蛋白质免疫印迹及挽救实验来探索靶标结合关系和调控机制。
CircCCT2在HNSCC组织和细胞中显著上调。高CircCCT2水平与晚期T分期、N分期、临床分期及不良预后相关。在功能上，我们证实CircCCT2在体外和体内均促进HNSCC的发展。机制上，作为竞争性内源性RNA（ceRNA）或miRNA海绵，CircCCT2直接与miR-146a-5p结合并提高白细胞介素-1受体相关激酶1（IRAK1）水平，从而通过驱动上皮-间质转化（EMT）增强HNSCC的恶性发展。
CircCCT2通过miR-146a-5p/IRAK1轴促进HNSCC发展，表明CircCCT2是HNSCC的潜在生物标志物和治疗靶点。
