BCAT1 通过 PI3K-Akt 信号通路促进口腔鳞状细胞癌中的细胞增殖、迁移和侵袭。
BCAT1 promotes cell proliferation, migration, and invasion via the PI3K-Akt signaling pathway in oral squamous cell carcinoma.
发表日期:2024 Jul 26
作者:
Zhenying Yuan, Ming Li, Zhangui Tang
来源:
ORAL DISEASES
摘要:
目的分析支链氨基酸转氨酶1(BCAT1)在口腔鳞状细胞癌(OSCC)中的表达及生物学功能。采用实时荧光定量PCR和免疫组化方法分析BCAT1蛋白在口腔鳞状细胞癌和正常口腔组织中的表达。根据患者的临床病理信息,分析BCAT1蛋白表达与其他临床病理因素的关系。采用实时PCR和蛋白质印迹法分别分析正常人口腔角质形成细胞(HOK)和人OSCC细胞中BCAT1基因和蛋白的表达。 BCAT1过表达或敲低后,分别通过CCK8、流式细胞术、伤口愈合和Transwell侵袭实验分析人OSCC细胞的增殖、细胞周期、迁移和侵袭。在OSCC细胞中添加BCAT1抑制剂EGR240后,分析OSCC细胞增殖、迁移和侵袭能力的变化。基于TCGA数据库,获得BCAT1相关和BCAT1结合基因所涉及的信号通路,用于京都基因和基因组百科全书(KEGG)分析,并通过蛋白质印迹分析验证。抑制 PI3K 后,通过蛋白质印迹分析分析 BCAT1 对 PI3K-Akt 信号通路下游磷酸化蛋白表达的影响。分析OSCC细胞中BCAT1与EMT相关蛋白表达量的关系。OSCC组织中BCAT1基因及蛋白表达均上调,且与OSCC患者的病理分级呈正相关。与正常口腔角质形成细胞相比,OSCC细胞中BCAT1基因和蛋白表达上调。 BCAT1过表达促进OSCC细胞的增殖、迁移和侵袭。 BCAT1敲低或抑制可降低OSCC细胞的增殖、迁移和侵袭能力。生物信息学分析和Western blot结果显示,BCAT1可以调节PI3K-Akt信号通路的激活,促进OSCC细胞上皮间质转化(EMT)。BCAT1可以通过PI3K促进OSCC细胞的增殖、迁移和侵袭。 -Akt 信号通路,这是 OSCC 的潜在治疗靶点。© 2024 John Wiley
To analyze the expression, biological function of branched chain amino-acid transaminase 1 (BCAT1) in oral squamous cell carcinoma (OSCC).Real-time PCR and immunohistochemistry were used to analyze the expression of BCAT1 protein in OSCC and normal oral tissues. Based on the clinicopathological information of patients, the relationship between the expression of BCAT1 protein and other clinicopathological factors was analyzed. Real-time PCR and western blot assays were used to analyze the expression of BCAT1 gene and protein in normal human oral keratinocytes (HOK) and human OSCC cells, respectively. After BCAT1 overexpression or knockdown, the proliferation, cell cycle, migration, and invasion of human OSCC cells were analyzed by CCK8, flow cytometry, wound healing, and transwell invasion assays, respectively. After adding the BCAT1 inhibitor EGR240 to OSCC cells, the changes in cell proliferation, migration, and invasion ability in OSCC cells were analyzed. Based on the TCGA database, the involved signal pathway in BCAT1-related and BCAT1-binding genes was obtained for Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, verified by western blot assays. After inhibiting PI3K, the effect of BCAT1 on the expression of the downstream phosphorylated protein of the PI3K-Akt signaling pathway was analyzed by western blot assays. The relationship between the expression of BCAT1 and EMT-related protein of OSCC cells was also analyzed.The expression of BCAT1 gene and protein were upregulated in OSCC tissue, which positively correlated with the pathological grade of patients with OSCC. Compared with normal oral keratinocytes, BCAT1 gene and protein were upregulated in OSCC cells. BCAT1 overexpression promoted the proliferation, migration, and invasion of OSCC cells. BCAT1 knockdown or inhibition could reduce the proliferation, migration, and invasion abilities of OSCC cells. The results of bioinformatics analysis and Western bolt showed that BCAT1 could regulate the activation of PI3K-Akt signaling pathway, and promote epithelial-mesenchymal transition (EMT) of OSCC cells.BCAT1 could promote the proliferation, migration, and invasion of OSCC cells via PI3K-Akt signaling pathway, which is a potential therapeutic target for OSCC.© 2024 John Wiley & Sons Ltd.