RUN和FYVE结构域蛋白1在胰腺癌中的表达特征及功能作用
Expression characteristics and functional role of RUN and FYVE domain containing 1 in pancreatic cancer
钱志鑫 1李俊强 1宋扬 1苏海川1
作者信息
- 1. 空军军医大学唐都医院肿瘤科,陕西西安 710038
- 折叠
摘要
目的 探究RUN和FYVE结构域蛋白1(RUFY1)在胰腺癌中的表达特征及功能作用.方法 通过分析癌症基因组图谱、临床蛋白质组肿瘤分析协作组、基因表达综合数据库等,探究RUFY1在胰腺癌中mRNA、蛋白的表达水平以及与胰腺癌患者预后关系.采用免疫组织化学染色比对胰腺癌患者肿瘤组织与正常胰腺组织中RUFY1蛋白表达水平.在胰腺癌细胞系中敲低RUFY1,并通过肿瘤成球、CCK-8、克隆形成实验验证RUFY1在胰腺癌细胞系中发挥的功能与作用.联合CTRP和PRISM等数据库探究RUFY1与部分抗肿瘤药物敏感性的关系.结果 通过分析公共数据库发现,与正常胰腺组织相比,胰腺癌肿瘤组织中RUFY1 mRNA和蛋白表达水平显著升高(P＜0.05,P＜0.01);RUFY1的高表达与胰腺癌患者的预后呈显著负相关(P＜0.05).免疫组织化学染色结果表明,相较于癌旁组织,RUFY1蛋白表达水平在胰腺癌肿瘤组织中升高.肿瘤成球、CCK-8、克隆形成实验结果显示RUFY1敲低会显著抑制胰腺癌细胞系的增殖功能(P＜0.01).由CTRP和PRISM数据库分析得出,低RUFY1 表达的患者对 PD318088(P＜0.01)、RITA(P＜0.01)、selumetinib(P＜0.05)、AZD8931(P＜0.01)等药物更加敏感.结论 RUFY1 mRNA及蛋白水平在胰腺癌肿瘤组织中升高,RUFY1的高表达与胰腺癌患者的预后呈负相关,敲低RUFY1可抑制胰腺癌细胞系的增殖能力,RUFY1有望成为用来预测临床用药治疗敏感性的靶点.
Abstract
Objective To investigate the expression characteristics and functional role of RUN and FYVE domain containing 1(RUFY1)in pancreatic cancer.Methods The mRNA and protein expression levels of RUFY1 in pancreatic cancer and its relationship with the prognosis of pancreatic cancer patients were investigated by analyzing The Cancer Genome Atlas,Clinical Proteomic Tumor Analysis Consortium,Gene Expression Omnibus and other databases.Immunohistochemical staining was used to compare the expression of RUFY 1 protein in tumor tissues of pancreatic cancer patients and normal pancreatic tissues.RUFY1 was knocked down in pancreatic cancer cell lines,and the function and effect of RUFY 1 in pancreatic cancer cell lines were verified by tumor sphere formation,CCK-8 and clonal formation assays.The relationship between RUFY 1 and the sensitivity of some antitumor drugs was investigated by combining CTRP and PRISM databases.Results Compared with normal pancreatic tissues,the mRNA and protein expression levels of RUFY1 in pancreatic cancer tissues were significantly increased(P＜0.05,P＜0.01).The high expression of RUFY1 was negatively correlated with the prognosis of pancreatic cancer patients(P＜0.05).Immunohistochemical staining showed that the expression level of RUFY1 protein was increased in pancreatic cancer tissues compared with adjacent tissues.The results of tumor sphere formation,CCK-8 and clonal formation assays showed that RUFY1 knockdown could significantly inhibit the proliferation of pancreatic cancer cell lines(P＜0.01).According to CTRP and PRISM databases,patients with low RUFY1 expression were more sensitive to PD318088(P＜0.01),RITA(P＜0.01),selumetinib(P＜0.05),and AZD8931(P＜0.01).Conclusion The mRNA and protein levels of RUFY1 are increased in pancreatic cancer tissues,and the high expression of RUFY 1 is negatively correlated with the prognosis of pancreatic cancer patients.Knockdown of RUFY1 can inhibit the proliferation ability of pancreatic cancer cell lines,and RUFY1 is expected to be used as a target to predict the sensitivity of clinical drug therapy.
关键词
RUN和FYVE结构域蛋白1/胰腺癌/药物敏感性/增殖能力Key words
RUN and FYVE domain containing 1/pancreatic cancer/drug sensitivity/proliferation ability引用本文复制引用
基金项目
国家自然科学基金(81372255)
国家自然科学基金(31571414)
出版年
2024
国家科技期刊平台
NSTL
万方数据