Selenoprotein K Mediates the Proliferation, Migration, and Invasion of Human Choriocarcinoma Cells by Negatively Regulating Human Chorionic Gonadotropin Expression via ERK, p38 MAPK, and Akt Signaling Pathway
Selenoprotein K Mediates the Proliferation, Migration, and Invasion of Human Choriocarcinoma Cells by Negatively Regulating Human Chorionic Gonadotropin Expression via ERK, p38 MAPK, and Akt Signaling Pathway
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硒蛋白 K 通过 ERK、p38 MAPK 和 Akt 信号通路负调控人绒毛膜促性腺激素表达，介导人绒毛膜癌细胞的增殖、迁移和侵袭
DOI：
10.1007/s12011-017-1155-3
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发表时间：
2018-07-01
影响因子：
3.9
通讯作者：
Li, Hui
中科院分区：
文献类型：
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作者：
Li, Mengdi;Cheng, Wanpeng;Li, Hui
硒蛋白K(SelenoProtein K，SELK)是硒蛋白家族的一员，是一种单一的内质网跨膜蛋白。虽然SELK的过表达抑制了人胃癌BGC-823细胞的黏附和迁移，但SELK在人绒毛膜癌中的作用尚不清楚。本研究检测了SELK在三种CCA细胞系BeWo、JEG-3和JAR中的表达水平。免疫印迹法检测沉默或过表达SELK对人绒毛膜促性腺激素β亚单位(β-hCG)表达的影响。结果表明，β-hCG的蛋白水平受SELK基因表达上调或下调的交互调节(P<；n0.05；#p<；n0.05)。然后使用细胞计数试剂盒8(CCK-8)、伤口愈合和Transwell小室检测SELK表达降低或过表达的JEG-3细胞的增殖、迁移和侵袭能力。我们发现，JEG-3细胞中SELK的缺失显著增加了这些细胞的活性。相反，在JEG-3细胞中过表达SELK抑制了这些表型。此外，还检测了下调或上调β-hCG后SELK的表达。令人惊讶的是，我们发现SELK水平受到β-hCG的影响(*P<；n0.05；#P<；n0.05)。检测β-hCG每次过表达和下调后细胞的增殖、迁移和侵袭能力。结果证实β-hCG对人绒毛膜癌具有启动子作用。此外，还发现ERK/p38MAPK和Akt信号通路参与了这些细胞功能。这项工作表明，SELK可能通过ERK、p38MAPK和AKT信号通路负向调节β-hCG的表达，从而在人绒毛癌细胞中发挥肿瘤抑制作用。这些发现表明，硒蛋白K可能成为体外治疗绒毛膜癌的新靶点。
Selenoprotein K (SelK), a member of selenoprotein family, is identified as a single endoplasmic reticulum (ER) transmembrane protein. Although over-expression of SelK inhibits adherence and migration of human gastric cancer BGC-823 cells, the effects of SelK in human choriocarcinoma (CCA) are not well understood. In this study, the expression levels of SelK in three CCA cell lines, BeWo, JEG-3, and JAR, were examined. The effects of silencing or over-expressing SelK on expression of human chorionic gonadotropin beta subunit (β-hCG) were detected by western blotting. The results show that the protein level of β-hCG was reciprocally regulated by down- or up-regulation of SelK (*P< 0.05; #P< 0.05). The proliferative, migratory, and invasive capabilities of JEG-3 cells with reduced or over-expressed SelK were then tested using the cell counting kit-8 (CCK-8), wound healing, and transwell chamber assays. We found that these cellular activities were markedly increased by the loss of SelK in JEG-3 cells. Conversely, over-expressing SelK in JEG-3 cells suppressed these phenotypes. In addition, SelK expression after down- or up-regulation of β-hCG was also measured. Surprisingly, we found that level of SelK was affected by β-hCG (*P< 0.05; #P< 0.05). The proliferation, migration, and invasion were determined in JEG-3 cells after each over-expression and reduction of β-hCG. The results confirmed that β-hCG functions as a promoter of human choriocarcinoma. Furthermore, ERK/p38 MAPK and Akt signaling pathways were found to involve in these cellular functions. This work suggests that SelK may act as a tumor suppressor in human choriocarcinoma cells by negatively regulating β-hCG expression via ERK, p38 MAPK, and Akt signaling pathways. These findings revealed that selenoprotein K may serve as a novel target for human choriocarcinoma therapy in vitro.