背景:肺腺癌(LUAD)是一种具有代谢异常的致命疾病。S100钙结合蛋白A2(S100A2)的失调,S100蛋白家族的一员,与各种癌症的发展有关。S100A2对LUAD发生和转移的影响,然而,尚未报告。本文研究了S100A2对LUAD细胞转移的作用机制。
方法:通过生物信息学和qRT-PCR分析TFAP2A和S100A2在LUAD组织和细胞中的表达,分别。对S100A2进行富集途径分析。生物信息学分析确定了TFAP2A和S100A2之间的结合关系,并通过双荧光素酶和染色质免疫沉淀实验验证了它们的相互作用。使用细胞计数试剂盒-8(CCK-8)测定细胞活力。进行transwell测定以分析细胞的侵袭和迁移。免疫荧光检测波形蛋白和E-cadherin的表达,蛋白印迹法检测MMP-2、MMP-9、GLS、和GLUD1。试剂盒测量了NADPH/NADP比率,谷胱甘肽(GSH)/谷胱甘肽二硫化物(GSSG)水平,还有谷氨酰胺的含量,α-KG,还有谷氨酸.
结果:S100A2在LUAD组织和细胞中上调,和S100A2介导谷氨酰胺代谢诱导LUAD转移。此外,在S100A2的上游发现了转录调节子TFAP2A,在LUAD中TFAP2A表达上调,这表明TFAP2A促进了S100A2的表达。拯救实验发现,上调S100A2可以逆转沉默TFAP2A对谷氨酰胺代谢和细胞转移的抑制作用。
结论:结论:通过调节谷氨酰胺代谢,TFAP2A/S100A2轴促进LUAD转移.这表明靶向S100A2可能有益于LUAD治疗。
BACKGROUND: Lung adenocarcinoma (LUAD) is a fatal disease with metabolic abnormalities. The dysregulation of S100 calcium-binding protein A2 (S100A2), a member of the S100 protein family, is connected to the development of various cancers. The impact of S100A2 on the LUAD occurrence and metastasis, however, has not yet been reported. The functional mechanism of S100A2 on LUAD cell metastasis was examined in this article.
METHODS: The expression of TFAP2A and S100A2 in LUAD tissues and cells was analyzed by bioinformatics and qRT-PCR, respectively. The enrichment pathway analysis was performed on S100A2. Bioinformatics analysis determined the binding relationship between TFAP2A and S100A2, and their interaction was validated through dual-luciferase and chromatin immunoprecipitation experiments. Cell viability was determined using cell counting kit-8 (CCK-8). A transwell assay was performed to analyze the invasion and migration of cells. Immunofluorescence was conducted to obtain vimentin and E-cadherin expression, and a western blot was used to detect the expression of MMP-2, MMP-9, GLS, and GLUD1. The kits measured the NADPH/NADP ratio, glutathione (GSH)/glutathione disulfide (GSSG) levels, and the contents of glutamine, α-KG, and glutamate.
RESULTS: S100A2 was upregulated in LUAD tissues and cells, and S100A2 mediated glutamine metabolism to induce LUAD metastasis. Additionally, the transcriptional regulator TFAP2A was discovered upstream of S100A2, and TFAP2A expression was upregulated in LUAD, which indicated that TFAP2A promoted the S100A2 expression. The rescue experiment found that upregulation of S100A2 could reverse the inhibitory effects of silencing TFAP2A on glutamine metabolism and cell metastasis.
CONCLUSIONS: In conclusion, by regulating glutamine metabolism, the TFAP2A/S100A2 axis facilitated LUAD metastasis. This suggested that targeting S100A2 could be beneficial for LUAD treatment.