Department of gynaecology and obstetrics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
Department of Pathology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, 330006, China.
Exp Cell Res. 2020 Mar 1;388(1):111809. doi: 10.1016/j.yexcr.2019.111809. Epub 2019 Dec 28.
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.
富含核小体酶结构域蛋白 1（SND1）已知参与多种人类癌症的进展。然而，SND1 在宫颈癌中的作用尚不清楚。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，高 SND1 表达与宫颈癌患者的致瘤表型和更短的生存密切相关。功能分析表明，SND1 敲低抑制了宫颈癌细胞在体外的迁移和侵袭能力。此外，异种移植实验表明，沉默宫颈癌细胞中的 SND1 可抑制体内肺转移。进一步的研究表明，SND1 通过增强 FOXA2 的表达抑制了宫颈癌细胞的上皮间质转化（EMT）。此外，SND1 在宫颈癌中的促转移作用至少部分依赖于 FOXA2 抑制。在机制上，我们发现 SND1 诱导的 FOXA2 泛素化导致降解，由 E3 连接酶酶 Smurf1 介导。总之，SND1 在宫颈癌转移中起着关键作用，我们提供的证据表明 SND1 可能是宫颈癌的预后和治疗靶点。
