GFPT2促进前列腺癌细胞迁移的作用和机制研究  

The role and mechanism of GFPT2 in promoting the migration of prostate cancer cells

作　　者：崔金龙 习舒 王丹琦 史明慧 刘姝言 王诗淳 刘桂子 明道靖 袁帅 曾宪涛 CUI Jinlong;XI Shu;WANG Danqi;SHI Minghui;LIU Shuyan;WANG Shichun;LIU Guizi;MING Daojing;YUAN Shuai;ZENG Xiantao(Center for Evidence-Based and Translational Medicine,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;Department of Urology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China)

机构地区：[1]武汉大学中南医院循证与转化医学中心,武汉430071 [2]武汉大学中南医院泌尿外科,武汉430071

出　　处：《医学新知》2025年第2期175-182,共8页New Medicine

基　　金：国家自然科学基金面上项目(82373411);湖北省自然科学基金面上项目(2023AFB742)。

摘　　要：目的研究谷氨酰胺果糖-6-磷酸转氨酶2(glutamine fructose-6-phosphate transaminase 2,GFPT2)对前列腺癌细胞迁移的影响及其潜在的分子机制。方法采用qRT-PCR检测RWPE-1细胞及五种人前列腺癌细胞系中GFPT2基因mRNA的表达水平;分析人类蛋白质图谱(The Human Protein Atlas,HPA)中前列腺正常组织和癌组织的GFPT2免疫组化数据;利用siRNA构建GFPT2基因干扰的细胞模型;利用Transwell实验和细胞划痕实验评估细胞迁移能力;通过Western blot检测细胞上皮-间充质转化(epithelial-mesenchymal transition,EMT)相关生物标志物的变化。结果与RWPE-1细胞相比,高转移潜能的前列腺癌细胞系PC3和DU145中GFPT2 mRNA的表达水平显著升高。HPA数据库GFPT2免疫组化数据表明,前列腺癌组织中GFPT2的蛋白水平明显高于正常前列腺组织。干扰GFPT2明显降低了前列腺癌细胞的O-GlcNAc糖基化水平。体外实验表明,干扰GFPT2显著抑制了前列腺癌细胞的迁移能力,并导致EMT相关蛋白E-cadherin的水平上调,N-cadherin和Vimentin的水平下调。结论GFPT2在前列腺癌中表达升高并促进肿瘤细胞迁移,有望成为抑制前列腺癌转移的新靶点。Objective To explore the role of glutamine fructose-6-phosphate transaminase 2(GFPT2)in the migration of prostate cancer cells and its underlying molecular mechanism.Methods The mRNA expression of GFPT2 in RWPE-1 and five human prostate cancer cell lines was detected by qRT-PCR.Analyzing the immunohistochemistry data of GFPT2 from the Human Protein Atlas (HPA) for normal prostate tissue and prostate cancer tissue. The GFPT2 knockdown cell modelswere established using siRNA. Cell migration ability was assessed through Transwell assay and Cell scratchassay. The biomarkers of epithelial-mesenchymal transition (EMT) were determined by Western blot. ResultsCompared with RWPE-1 cells, GFPT2 mRNA expression was significantly upregulated in high-metastaticprostate cancer cell lines (PC3 and DU145). Immunohistochemistry data from the HPA indicated that theexpression level of GFPT2 in prostate cancer tissue was significantly higher than in normal prostate tissue.In vitro, GFPT2 knockdown markedly reduced O-GlcNAcylation levels in prostate cancer cells. Additionally,GFPT2 knockdown significantly suppressed the migration of prostate cancer cells, upregulated the proteinlevel of E-cadherins, and downregulated the protein levels of N-cadherin and Vimentin. Conclusion GFPT2is upregulated in prostate cancer and promotes tumor cell migration, making it a promising new target forinhibiting prostate cancer metastasis.

关 键 词：前列腺癌 GFPT2 O-GlcNAc糖基化 迁移 上皮-间充质转化 

分 类 号：R737.25[医药卫生—肿瘤]