Down-regulation of Glutathione Peroxidase 4 in Oral Cancer Inhibits Tumor Growth Through SREBP1 Signaling
Down-regulation of Glutathione Peroxidase 4 in Oral Cancer Inhibits Tumor Growth Through SREBP1 Signaling
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DOI：
10.21873/anticanres.14944
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发表时间：
2021-04-01
影响因子：
2
通讯作者：
Sakashita, Hideaki
中科院分区：
文献类型：
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作者：
Fukuda, Masakatsu;Ogasawara, Yudai;Sakashita, Hideaki
背景/目的：本研究旨在探讨谷胱甘肽过氧化物酶4（GPX 4）在口腔癌细胞固醇调节元件结合蛋白（SREBPs）-增殖通路中的作用及其在口腔癌组织中的表达。结果：SAS细胞中GPX 4 mRNA和蛋白表达水平最高，而GPX 4基因表达水平最低。使用GPX 4 siRNA在SAS细胞（一种人口腔鳞状细胞癌细胞系）中的GPX 4敲低导致细胞数量减少，这似乎是由于非凋亡性细胞死亡如铁凋亡。此外，在SAS细胞中，GPX 4敲低明显下调SREBP。GPX 4在人口腔鳞癌细胞膜上呈阳性表达，且与p53免疫阳性表达相关。结论：GPX 4在口腔鳞癌细胞增殖中起重要作用。
Background/Aim: This study aimed to elucidate the role of glutathione peroxidase 4 (GPX4) on the sterol regulatory element binding proteins (SREBPs)-proliferation pathway in oral cancer cells, and determine its protein expression in oral cancer tissues.Materials and Methods: Quantitative RT-PCR and immunoblot analysis were carried out. Cell viability assay, apoptosis detection assay, immunohistochemistry and GPX4 knockdown were performed.Results: The levels of both GPX4 mRNA and protein were highest in SAS cells. GPX4 knockdown in SAS cells, a human oral squamous cell carcinoma cell line, using GPX4 siRNA resulted in a reduction in cell number, which appeared to be due to non-apoptotic cell death such as ferroptosis. Furthermore, SREBP was clearly down-regulated by GPX4 knockdown in SAS cells. Immunopositivity for GPX4 was revealed on the membrane of human oral squamous cell carcinoma cells, and this was correlated with p53 immunoreactivity.Conclusion: GPX4 appears to play an important role in oral cancer proliferation.