Selenoprotein S regulates tumorigenesis of Clear Cell Renal Cell Carcinoma through AKT/ GSK3β/NF-κB signaling pathway.
Selenoprotein S regulates tumorigenesis of Clear Cell Renal Cell Carcinoma through AKT/ GSK3β/NF-κB signaling pathway.
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DOI：
10.1016/j.gene.2022.146559
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发表时间：
2022-05
期刊：
影响因子：
3.5
通讯作者：
Huajie Mao;Ya Zhao;Li Lei;Yanxia Hu;Ha Zhu;Runzhi Wang;Dongsheng Ni;Jianing Liu;Lei Xu
中科院分区：
文献类型：
--
作者：
Huajie Mao;Ya Zhao;Li Lei;Yanxia Hu;Ha Zhu;Runzhi Wang;Dongsheng Ni;Jianing Liu;Lei Xu
肾透明细胞癌（Clear cell renal cell carcinoma，ccRCC）是泌尿生殖系统最致命的肿瘤之一。硒蛋白S（Selenoprotein S，SELS）广泛表达于人体组织中，参与调节内质网的稳态和炎症反应。然而，SELS在ccRCC中的生物学作用仍不清楚。在这项研究中，我们发现SELS在ccRCC中的表达显著升高，并与多种临床病理特征相关。在786-O细胞中，SELS的过表达可促进细胞增殖，抑制细胞凋亡，而沉默SELS则相反。进一步的机制研究表明，SELS通过激活AKT/GSK 3 β/NF-κB信号通路促进细胞增殖，抑制细胞凋亡。此外，SELS还可以通过阻止遍在蛋白酶体介导的降解来稳定c-Myc。有趣的是，我们发现SELS还可以抑制ccRCC细胞的迁移，可能是通过抑制上皮-间充质转化（EMT）。结论：SELS通过AKT/GSK 3 β/NF-κB信号通路和EMT促进肾细胞癌的发生发展，抑制细胞凋亡和迁移。
Clear cell renal cell carcinoma (ccRCC) is one of the most lethal genitourinary tumors with rapid progression and metastasis. Selenoprotein S (SELS), which is broadly expressed in human tissues, has been reported to be involved in ER homeostasis and inflammation. However, the biological roles of SELS in ccRCC remain unclear. In this study, we found that SELS expression was significantly higher in ccRCC and correlated with multiple clinicopathological features. Overexpression of SELS could promote cell proliferation and inhibit apoptosis in 786-O cells, whereas silence of SELS elicited opposite effect. Further mechanistic studies revealed that SELS enhanced cell proliferation and inhibited apoptosis through activating AKT/GSK3β/NF-κB signaling pathway. Besides, SELS could stabilize c-Myc by preventing ubiquitin–proteasome-mediated degradation. Interestingly, we found that SELS could also inhibit migration of ccRCC cell likely through repressing epithelial–mesenchymal transition (EMT). Collectively, our findings suggested that SELS promoted tumor progression, and inhibited apoptosis and migration through AKT/GSK3β/NF-κB signaling pathway and EMT in ccRCC.