结直肠癌（CRC）的肿瘤进展严重影响患者的预后。对于晚期CRC患者，仍需不断探索更有效的靶向治疗药物。环状RNA（circRNA）参与肿瘤生物学的调节。我们筛选了circAURKA，通过之前的高通量RNA测序，该蛋白在CRC中显着高表达。体外实验研究circRNA对HCT116和SW480细胞增殖和转移的影响。此外，我们还利用EdU实验、Transwell实验、裸鼠异种移植肿瘤模型和裸鼠尾静脉转移模型来检测circAURKA对CRC增殖和转移的影响。从机制上讲，我们进行了荧光原位杂交（FISH）、RNA Pull-down、RNA免疫沉淀（RIP）、蛋白质共免疫沉淀（co-IP）实验和动物模型来证实circAURKA的潜在机制。 CircAURKA在CRC组织和结直肠细胞中显着高表达，主要存在于细胞质中。 circRNA在体外和体内促进CRC细胞的增殖和转移。从分子机制来看，circAURKA通过促进ACLY与CTNNB1蛋白的相互作用，抑制CTNNB1蛋白的降解，从而促进CRC细胞的增殖和转移。此外，circAURKA 稳定性受到 m6A 甲基化修饰的调节。该研究表明，circAURKA通过抑制CTNNB1蛋白降解促进CRC的增殖和转移，为开发控制CRC进展的靶向药物提供基础。© 2024。作者，获得Springer Nature Limited独家许可。

Tumor progression of colorectal cancer (CRC) seriously affects patient prognosis. For CRC patients with advanced-stage disease, it is still necessary to continuously explore more effective targeted therapeutic drugs. Circular RNAs (circRNAs) are involved in the regulation of tumor biology. We screened circAURKA, which was significantly highly expressed in CRC by previous high-throughput RNA sequencing. In vitro experiments were performed to investigate the effect of the circRNA on the proliferation and metastasis of HCT116 and SW480 cells. In addition, we used the EdU assay, Transwell assay, nude mouse xenograft tumor model and nude mouse tail vein metastasis model to examine the effect of circAURKA on the proliferation and metastasis of CRC. Mechanistically, fluorescent in situ hybridization (FISH), RNA pull-down, RNA immunoprecipitation (RIP), protein coimmunoprecipitation (co-IP) experiments and animal models were performed to confirm the underlying mechanisms of circAURKA. CircAURKA was significantly highly expressed in CRC tissues and colorectal cells and mainly present in the cytoplasm. The circRNA promoted the proliferation and metastasis of CRC cells in vitro and in vivo. In terms of the molecular mechanism, circAURKA inhibited the degradation of the CTNNB1 protein by promoting the interaction between ACLY and the CTNNB1 protein, thereby promoting the proliferation and metastasis of CRC cells. In addition, circAURKA stability was regulated by m6A methylation modification. This study revealed that circAURKA promoted the proliferation and metastasis of CRC by inhibiting CTNNB1 protein degradation, providing a basis for the development of targeted drugs to control CRC progression.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.