口腔鳞状细胞癌（OSCC）是一种世界范围内流行的癌症，具有独特的地区流行率。尽管诊断和治疗取得了进步，但患者的 5 年生存率改善有限。更深入地了解 OSCC 发病机制，尤其是其分子基础，对于改进检测、预防和治疗至关重要。在此背景下，非编码 RNA，例如环状 RNA (circRNA)，已被认为是 OSCC 进展中的关键调节因子和潜在生物标志物。我们的研究强调通过对 OSCC 患者组织转录组进行深度测序，发现了以前未表征的 circRNA，包括 SNX5 基因衍生的 circRNA，circSNX5。我们使用结构特异性和定量 PCR 分析确定了 circSNX5 的肿瘤特异性表达及其与患者生存的强相关性。体外和体内实验强调了 circSNX5 RNA 在癌症生长和转移中的调节作用。此外，我们的组学分析和功能分析表明，ADAM10 是 circSNX5 介导的癌症进展中的关键效应子，circSNX5 通过海绵 miR-323 维持 ADAM10 表达。这种新型的 circRNA-miRNA-mRNA 调控轴对口腔癌的进展和恶性肿瘤有显着贡献。此外，我们发现 circSNX5 RNA 是通过前 mRNA 的非常规顺序反向剪接产生的，这一过程受到 RNA 结合蛋白 STAU1 的负调控。这一发现为我们对真核转录组中外显子 circRNA 生物发生的理解增加了一个新的维度。总的来说，我们的研究结果对新型 circRNA 进行了详细的机制剖析和功能解释，揭示了非编码转录组在癌症生物学中的作用，并可能为创新治疗策略铺平道路。© 2024。作者。

Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide, exhibiting unique regional prevalence. Despite advancements in diagnostics and therapy, the 5-year survival rate for patients has seen limited improvement. A deeper understanding of OSCC pathogenesis, especially its molecular underpinnings, is essential for improving detection, prevention, and treatment. In this context, noncoding RNAs, such as circular RNAs (circRNAs), have gained recognition as crucial regulators and potential biomarkers in OSCC progression. Our study highlights the discovery of previously uncharacterized circRNAs, including a SNX5 gene-derived circRNA, circSNX5, through deep sequencing of OSCC patient tissue transcriptomes. We established circSNX5's tumor-specific expression and its strong correlation with patient survival using structure-specific and quantitative PCR analyses. In vitro and in vivo experiments underscored circSNX5 RNA's regulatory role in cancer growth and metastasis. Further, our omics profiling and functional assays revealed that ADAM10 is a critical effector in circSNX5-mediated cancer progression, with circSNX5 maintaining ADAM10 expression by sponging miR-323. This novel circRNA-miRNA-mRNA regulatory axis significantly contributes to oral cancer progression and malignancy. Moreover, we discovered that circSNX5 RNA is produced via noncanonical sequential back-splicing of pre-mRNA, a process negatively regulated by the RNA-binding protein STAU1. This finding adds a new dimension to our understanding of exonic circRNA biogenesis in the eukaryotic transcriptome. Collectively, our findings offer a detailed mechanistic dissection and functional interpretation of a novel circRNA, shedding light on the role of the noncoding transcriptome in cancer biology and potentially paving the way for innovative therapeutic strategies.© 2024. The Author(s).