摘要
目的分析G蛋白偶联受体19(GPR19)在前列腺癌(PCa)中的表达情况,探究GPR19参与PCa进展的机制。方法利用TCGA、Oncomine数据库分析GPR19在PCa中的表达水平及临床病理信息。qPCR及Western blot检测PCa细胞系中GPR19的mRNA及蛋白的表达水平并验证相关通路中的关键分子,EdU实验验证敲低GPR19对肿瘤细胞增殖的影响。结果生物信息学分析显示GPR19基因在PCa样本中表达增高,且GPR19基因表达与患者的年龄、无进展生存率、Gleason评分、TNM分期有关。单因素Cox分析显示Gleason评分、TNM分期和GPR19表达是PCa患者无进展生存的影响因素。qPCR和Western blot显示PCa细胞系中GPR19的表达高于正常前列腺上皮细胞RWPE-1,敲低GPR19后的PCa细胞增殖能力减弱。通路富集分析发现GPR19参与了PCa的细胞周期调控,实验证实敲低GPR19后PCa细胞中G2M信号检查点上的关键分子细胞周期蛋白依赖性激酶1(CDK1)表达降低,通路相关性分析显示GPR19同细胞周期蛋白依赖性激酶抑制剂3(CDKN3)基因相关性最高。结论GPR19在PCa中表达升高,并与多种临床信息相关,通过G2M信号检查点影响肿瘤细胞增殖,有望成为PCa的潜在治疗靶点。
Objective To analyze the expression of G protein-coupled receptor 19(GPR19)in prostate cancer(PCa),and explore the mechanism of GPR19 in prostate cancer.Methods TCGA and Oncomine online databases were used to analyze the expression level and clinicopathological information of GPR19 in PCa.Expression levels of GPR19 mRNA and protein in PCa cell lines were detected by qPCR and Western blot assay,and the key molecules in related pathways were verified.EdU assay was used to verify the effect of GPR19 knockdown on tumor cell proliferation.Results Database analysis showed that GPR19 gene expression was increased in PCa samples.GPR19 gene expression was related to patient′s age,disease-free survival rate,Gleason score and TNM stage.Univariate Cox analysis showed that Gleason score,TNM stage and GPR19 expression were the influencing factors of progression-free survival in PCa patients.qPCR and Western blot assay showed that GPR19 was expressed higher in PCa cell lines than that of normal prostate epithelial cell line,RWPE-1.EdU experiments verified that the proliferation ability of PCa cells was reduced after GPR19 knockdown.Pathway enrichment analysis showed that GPR19 was involved in cell cycle regulation of PCa.It was confirmed that knockdown of GPR19 reduced the expression of cyclin dependent kinase 1(CDK1),a key molecule at the G2M signaling checkpoint in PCa cells.Pathway correlation analysis showed that GPR19 had the highest correlation with CDKN3 gene.Conclusion The expression of GPR19 is increased in PCa and related to a variety of clinical information,which affects tumor cell proliferation through the G2M signaling checkpoint.GPR19 is expected to be a potential therapeutic target for PCa.
作者
刘帅兵
闫墨
王楷斌
杨阔
王玉琢
LIU Shuaibing;YAN Mo;WANG Kaibin;YANG Kuo;WANG Yuzhuo(Department of Urology,Tianjin Institute of Urology,the Second Hospital of Tianjin Medical University,Tianjin 300211,China)
出处
《天津医药》
CAS
北大核心
2022年第11期1128-1133,共6页
Tianjin Medical Journal
基金
天津市科技计划项目(18ZXDBSY00020)。
