Staphylococcal nuclease domain-containing protein 1 (SND1) is known to be involved in the progression of a variety of human cancers. However, the role of SND1 in cervical cancer remains unclear. Here, we found that the expression of SND1 in cervical cancer tissue was higher than that in normal cervical tissue. Importantly, high SND1 expression was closely associated with tumorigenic phenotype and shorter survival among cervical cancer patients. Functional assays demonstrated that SND1 knockdown inhibited the migration and invasion capabilities of cervical cancer cells in vitro. Additionally, a xenograft assay showed that silencing SND1 in cervical cancer cells suppressed lung metastasis in vivo. Further investigation revealed that knockdown of SND1 inhibited epithelial-to-mesenchymal transition (EMT) of cervical cancer cells by enhancing FOXA2 expression. Moreover, the pro-metastasis effect of SND1 in cervical cancer was at least in part dependent on FOXA2 inhibition. Mechanistically, we found that SND1-induced FOXA2 ubiquitination resulted in degradation, mediated by the E3 ligase enzyme Smurf1. In summary, SND1 plays a crucial role in cervical cancer metastasis, and we provide evidence that SND1 may serve as a prognostic and therapeutic target in cervical cancer.

中文翻译：

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SND1通过Smurf1介导的FOXA2降解促进宫颈癌细胞的侵袭和迁移。

已知含有葡萄球菌核酸酶结构域的蛋白质1（SND1）与多种人类癌症的进展有关。但是，尚不清楚SND1在宫颈癌中的作用。在这里，我们发现SND1在宫颈癌组织中的表达高于正常宫颈组织。重要的是，在宫颈癌患者中，高SND1表达与致瘤表型密切相关且生存期较短。功能测定表明，SND1敲低抑制了子宫颈癌细胞的迁移和侵袭能力。另外，异种移植测定法显示，使宫颈癌细胞中的SND1沉默可抑制体内肺转移。进一步的研究表明，敲低SND1可以通过增强FOXA2表达来抑制宫颈癌细胞的上皮向间充质转化（EMT）。此外，SND1在子宫颈癌中的促转移作用至少部分取决于FOXA2抑制作用。从机理上讲，我们发现SND1诱导的FOXA2泛素化导致降解，这是由E3连接酶Smurf1介导的。综上所述，SND1在子宫颈癌的转移中起着至关重要的作用，我们提供的证据表明SND1可以作为子宫颈癌的预后和治疗靶标。