BCAT1 promotes cell proliferation, migration, and invasion via the PI3K-Akt signaling pathway in oral squamous cell carcinoma.

IF 2.9 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Oral diseases Pub Date : 2025-02-01 Epub Date: 2024-07-26 DOI:10.1111/odi.15084
Zhenying Yuan, Ming Li, Zhangui Tang
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引用次数: 0

Abstract

Objectives: To analyze the expression, biological function of branched chain amino-acid transaminase 1 (BCAT1) in oral squamous cell carcinoma (OSCC).

Materials and methods: 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.

Results: 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.

Conclusions: BCAT1 could promote the proliferation, migration, and invasion of OSCC cells via PI3K-Akt signaling pathway, which is a potential therapeutic target for OSCC.

BCAT1 通过 PI3K-Akt 信号通路促进口腔鳞状细胞癌细胞的增殖、迁移和侵袭。
研究目的分析支链氨基酸转氨酶1(BCAT1)在口腔鳞状细胞癌(OSCC)中的表达和生物学功能:采用实时荧光定量PCR和免疫组织化学方法分析支链氨基酸转氨酶1(BCAT1)蛋白在OSCC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 蛋白的表达与其他临床病理因素之间的关系。采用实时PCR和Western印迹法分别分析了BCAT1基因和蛋白在正常人口腔角朊细胞(HOK)和人OSCC细胞中的表达情况。BCAT1过表达或敲除后,人OSCC细胞的增殖、细胞周期、迁移和侵袭分别通过CCK8、流式细胞仪、伤口愈合和透孔侵袭实验进行了分析。在OSCC细胞中加入BCAT1抑制剂EGR240后,分析了OSCC细胞增殖、迁移和侵袭能力的变化。在TCGA数据库的基础上,通过Western印迹实验验证了京都基因组百科全书(KEGG)的分析,获得了BCAT1相关基因和BCAT1结合基因所涉及的信号通路。抑制PI3K后,通过Western印迹分析了BCAT1对PI3K-Akt信号通路下游磷酸化蛋白表达的影响。还分析了BCAT1与OSCC细胞EMT相关蛋白表达的关系:结果:BCAT1基因和蛋白在OSCC组织中表达上调,与OSCC患者的病理分级呈正相关。与正常口腔角质细胞相比,BCAT1基因和蛋白在OSCC细胞中上调。BCAT1的过表达促进了OSCC细胞的增殖、迁移和侵袭。敲除或抑制 BCAT1 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 bolt结果表明,BCAT1可调控PI3K-Akt信号通路的激活,促进OSCC细胞的上皮-间质转化(EMT):结论:BCAT1可通过PI3K-Akt信号通路促进OSCC细胞的增殖、迁移和侵袭,是OSCC的潜在治疗靶点。
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来源期刊
Oral diseases
Oral diseases 医学-牙科与口腔外科
CiteScore
7.60
自引率
5.30%
发文量
325
审稿时长
4-8 weeks
期刊介绍: Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.
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