E3泛素连接酶BTBD3通过调节TYRO3/Wnt/β-catenin信号轴抑制结直肠癌的肿瘤发生。

IF 5.3 2区 医学 Q1 ONCOLOGY
Kai Ye, Peng-Cheng Wang, Yan-Xin Chen, Qiao-Zhen Huang, Pan Chi
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引用次数: 0

摘要

临床试验和研究表明,E3 泛素连接酶 BTBD3(BTB Domain Containing 3)是一种癌症相关基因。然而,BTBD3 在结直肠癌(CRC)中的作用及其内在机制尚未完全明了。在本研究中,我们发现 BTBD3 的 mRNA 和蛋白水平在 CRC 组织中降低,并与 TYPO3 和 Wnt/β-catenin 通路相关。我们的研究结果表明,circRAE1敲除和TYRO3过表达激活了Wnt/β-catenin信号通路和EMT过程相关标志物,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,过表达 BTBD3 可减少 CRC 细胞在体外的迁移和侵袭,并抑制肿瘤在体内的生长。我们的数据表明,BTBD3通过负调控circRAE1/miR-388-3p/TYRO3轴和Wnt/β-catenin通路抑制了CRC的进展。我们的数据进一步证实,BTBD3与β-catenin结合并泛素化,导致β-catenin降解,从而阻断了Wnt/β-catenin通路,抑制了CRC肿瘤的发生。该研究探讨了BTBD3参与CRC肿瘤发生的机制,为CRC的防治提供了新的理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
E3 ubiquitin ligase BTBD3 inhibits tumorigenesis of colorectal cancer by regulating the TYRO3/Wnt/β-catenin signaling axis.

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.

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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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