Background Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Siah E3 ubiquitin protein ligase 1 (Siah1) has been identified as a tumor suppressor gene and plays an important role in the development of malignant tumors. However, the potential role and molecular mechanism of Siah1 in the development and progression of CRC is still unclear. Methods To explore the role and molecular mechanism of Siah1 in the development and progression of CRC, we examined the expression of Siah1 in CRC tissue samples and analyzed its association with progression and prognosis in CRC. In addition, overexpression and knockdown of Siah1 was used to investigate its activity in CRC cells. We also use bioinformatics to analyze and verify the significant roles of Siah1 in critical signaling pathways of CRC. Results We found that the expression of Siah1 was significantly downregulated in CRC tissues, and low expression of Siah1 was associated with aggressive TNM staging and poor survival of CRC patients. Moreover, we revealed that overexpression of Siah1 in CRC cells markedly inhibited CRC cell proliferation and invasion in vitro and in vivo, while knockdown of Siah1 enhanced CRC cell proliferation and invasion. Furthermore, we found that Siah1 prohibited cell proliferation and invasion in CRC partially through promoting AKT (the serine-threonine protein kinase) and YAP (yes associated protein) ubiquitylation and proteasome degradation to regulate the activity of MAPK(mitogen-activated protein kinase 1), PI3K-AKT (phosphatidylinositol 3-kinase-the serine-threonine protein kinase) and Hippo signaling pathways. Conclusions These findings suggested that Siah1 is a novel potential prognostic biomarker and plays a tumor suppressor role in the development and progression of CRC.

中文翻译：

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Siah1 的下调通过调节 AKT 和 YAP 泛素化和蛋白酶体降解促进结直肠癌细胞增殖和迁移。

背景结直肠癌（CRC）是世界上最常见的恶性肿瘤之一。Siah E3泛素蛋白连接酶1（Siah1）已被鉴定为抑癌基因，在恶性肿瘤的发生发展中起重要作用。然而，Siah1 在 CRC 发生发展中的潜在作用和分子机制仍不清楚。方法 为探讨 Siah1 在 CRC 发生发展中的作用及其分子机制，我们检测了 Siah1 在 CRC 组织样本中的表达，并分析了其与 CRC 进展和预后的关系。此外，Siah1 的过表达和敲低用于研究其在 CRC 细胞中的活性。我们还使用生物信息学来分析和验证 Siah1 在 CRC 关键信号通路中的重要作用。结果我们发现Siah1的表达在CRC组织中显着下调，Siah1的低表达与CRC患者的侵袭性TNM分期和较差的生存率有关。此外，我们发现在 CRC 细胞中过表达 Siah1 显着抑制 CRC 细胞在体外和体内的增殖和侵袭，而 Siah1 的敲低增强了 CRC 细胞的增殖和侵袭。此外，我们发现Siah1部分通过促进AKT（丝氨酸-苏氨酸蛋白激酶）和YAP（yes相关蛋白）泛素化和蛋白酶体降解来调节MAPK（丝裂原活化蛋白激酶1）的活性来抑制CRC中的细胞增殖和侵袭。 ，PI3K-AKT（磷脂酰肌醇3-激酶-丝氨酸-苏氨酸蛋白激酶）和Hippo信号通路。