SEPHS1 promotes SMAD2/3/4 expression and hepatocellular carcinoma cells invasion.
SEPHS1 promotes SMAD2/3/4 expression and hepatocellular carcinoma cells invasion.
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SEPHS1促进SMAD2/3/4表达及肝癌细胞侵袭
DOI：
10.1186/s40164-021-00212-7
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发表时间：
2021-02-23
影响因子：
10.9
通讯作者：
Hua H
中科院分区：
文献类型：
--
作者：
Yang S;Zhang H;Yang H;Zhang J;Wang J;Luo T;Jiang Y;Hua H
肝细胞癌（HCC）是一种非常具有侵袭性的常见癌症。分泌的细胞因子转化生长因子-β（TGF-β）通过上皮间质转化和免疫逃避等多种机制促进癌症转移。典型的 TGF-β 信号传导主要由平滑肌肌动蛋白/母亲针对十五肢麻痹 (SMAD) 蛋白介导。本研究旨在探讨硒磷酸合成酶 1 (SEPHS1) 对 TGF-β/SMAD 信号传导的调节。采用免疫组化方法检测HCC及癌旁肝组织中SEPHS1的表达情况。采用Western blotting和定量逆转录PCR检测HCC细胞系中的蛋白和mRNA水平。通过transwell实验测定细胞迁移和侵袭。通过生物信息学分析确定 SEPHS1 在 HCC 中的表达及其与 HCC 患者生存的相关性。在这里，我们报道 SEPHS1 是 SMAD 蛋白的正调节因子。与邻近肝组织相比，HCC 中 SEPHS1 表达上调。 SEPHS1 敲低导致 HCC 细胞中 SMAD2/3/4 和间充质标志物（包括 snail、slug 和 N-cadherin）的表达降低。此外，SEPHS1敲低导致HCC细胞迁移和侵袭减少，并抑制TGF-β对HCC细胞迁移和侵袭的刺激。 HCC 细胞中 SEPHS1 的过度表达会促进细胞侵袭，这种情况可以通过 SMAD3 敲低来消除。最后，SEPHS1 的较高表达与 HCC 患者的不良预后相关，表现为总生存期和无病生存期下降。 SEPHS1 是 TGF-β/SMAD 信号传导的正调节因子，在 HCC 中表达上调。 SEPHS1 表达增加可能表明 HCC 患者预后不良。
Hepatocellular carcinoma (HCC) is one of the common cancers that are very aggressive. The secreted cytokine transforming growth factor-β (TGF-β) promotes cancer metastasis by multiple mechanisms such as epithelial-mesenchymal transition and immune evasion. The canonical TGF-β signaling is largely mediated by smooth muscle actin/mothers against decapentaplegic (SMAD) proteins. The current study aims to explore the regulation of TGF-β/SMAD signaling by selenophosphate synthetase 1 (SEPHS1). Immunohistochemistry was used to detect the expression of SEPHS1 in HCC and adjacent liver tissues. Western blotting and quantitative reverse-transcription PCR were used to detect the protein and mRNA levels in HCC cell lines. Cell migration and invasion were determined by transwell assay. Bioinformatic analysis was conducted to determine SEPHS1 expression in HCC and its correlation with the survival of HCC patients. Here we report that SEPHS1 is a positive regulator of SMAD proteins. SEPHS1 expression is up-regulated in HCC compared with adjacent liver tissues. SEPHS1 knockdown leads to decreased expression of SMAD2/3/4 and mesenchymal markers including snail, slug and N-cadherin in HCC cells. Furthermore, SEPHS1 knockdown results in a decrease in HCC cells migration and invasion, and suppresses the stimulation of HCC cells migration and invasion by TGF-β. Overexpression of SEPHS1 in HCC cells promotes cell invasion, which can be abrogated by SMAD3 knockdown. Lastly, higher expression of SEPHS1 is correlated with poor prognosis in HCC patients, as manifested by decreased overall survival and disease-free survival. SEPHS1 is a positive regulator of TGF-β/SMAD signaling that is up-regulated in HCC. Increased SEPHS1 expression may indicate poor prognosis for patients with HCC.
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