临床试验和研究表明，E3 泛素连接酶 BTBD3（BTB 结构域包含 3）是一种癌症相关基因。然而，BTBD3 在结直肠癌 (CRC) 中的作用和潜在机制尚未完全清楚。在此，我们的研究表明，结直肠癌组织中 BTBD3 的 mRNA 和蛋白水平降低，并与 TYPO3 和 Wnt/β-catenin 通路相关。我们的结果显示，circRAE1敲低和TYRO3过表达激活了Wnt/β-catenin信号通路和EMT过程相关标记，表明circRAE1/miR-388-3p/TYRO3轴通过激活Wnt/β-catenin信号通路加剧了CRC的肿瘤发生。此外，BTBD3的过表达在体外减少了CRC细胞的迁移和侵袭，并在体内抑制了肿瘤的生长。我们的数据表明，BTBD3 通过负调节 circRAE1/miR-388-3p/TYRO3 轴和 Wnt/β-catenin 通路来抑制 CRC 进展。我们的数据进一步证实，BTBD3结合并泛素化β-catenin并导致β-catenin降解，从而阻断Wnt/β-catenin通路并抑制CRC肿瘤发生。该研究探讨了BTBD3参与CRC肿瘤发生的机制，为CRC的防治提供新的理论依据。©2024。作者。

Clinical trials and studies have implicated that E3 ubiquitin ligase BTBD3 (BTB Domain Containing 3) is a cancer-associated gene. However, the role and underlying mechanism of BTBD3 in colorectal cancer (CRC) is not fully understood yet. Herein, our study demonstrated that the mRNA and protein levels of BTBD3 were decreased in CRC tissues and associated with TYPO3 and Wnt/β-catenin pathway. Our results showed that circRAE1 knockdown and TYRO3 overexpression activated Wnt/β-catenin signaling pathway and the EMT process-associated markers, indicating that circRAE1/miR-388-3p/TYRO3 axis exacerbated tumorigenesis of CRC by activating Wnt/β-catenin signaling pathway. In addition, overexpression of BTBD3 reduced CRC cell migration and invasion in vitro and inhibited tumor growth in vivo. Our data demonstrated that BTBD3 suppressed CRC progression through negative regulation of the circRAE1/miR-388-3p/TYRO3 axis and the Wnt/β-catenin pathway. Our data further confirmed that BTBD3 bound and ubiquitinated β-catenin and led to β-catenin degradation, therefore blocked the Wnt/β-catenin pathway and suppressed the CRC tumorigenesis. This study explored the mechanism of BTBD3 involved in CRC tumorigenesis and provided a new theoretical basis for the prevention and treatment of CRC.© 2024. The Author(s).