蛋白异构酶Pin1调控YB-1促进肿瘤细胞增殖  

Prolyl isomerase Pin1 regulates YB-1 and promotes tumor cell proliferation

作　　者：王佳欣 龙娟 董源源 童英[1] WANG Jia-Xin;LONG Juan;DONG Yuan-Yuan;TONG Ying(Center of Growth,Metabolism and Aging,Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education,College of Life Sciences,Sichuan University,Chengdu 610064,China)

机构地区：[1]四川大学生命科学学院生长代谢与衰老研究中心、生物资源与生态环境教育部重点实验室,成都610064

出　　处：《四川大学学报（自然科学版）》2024年第6期224-231,共8页Journal of Sichuan University(Natural Science Edition)

基　　金：国家自然科学基金(31771559)。

摘　　要：脯氨酰异构酶Pin1与肿瘤的发生发展密切相关.为探究Pin1调控肿瘤细胞增殖的信号途径,本文进行了免疫共沉淀和蛋白半衰期实验.结果显示,Pin1可以结合YB-1蛋白,增加其稳定性进而上调蛋白水平.克隆形成和细胞增殖检测实验(MTS)表明,Pin1可通过YB-1促进骨肉瘤、胰腺癌和结直肠癌细胞的增殖.在364种癌细胞系以及结直肠癌临床样本中,Pin1与YB-1的蛋白水平呈显著正相关.免疫组化染色分析也表明,在28例骨肉瘤、63例胰腺癌和67例结直肠癌临床样本中,Pin1与YB-1的蛋白水平存在显著正相关.Pin1-YB-1轴是一条新的影响肿瘤细胞增殖的信号途径,可能成为肿瘤治疗的新靶标.Peptidyl-prolyl cis/trans isomerase Pin1 has been proven to be closely related to tumor progres⁃sion.Here,we aimed to explore the signal pathway by which Pin1 regulates the proliferation of tumor cells,immunoprecipitation and protein half-life experiments were conducted.The results showed that Pin1 can bind to YB-1 protein by co-immunoprecipitation assay,increase its stability,and thereby upregulate its protein lev⁃els.Moreover,colony formation and cell proliferation assays(MTS)indicated that Pin1 promotes the prolif⁃eration of osteosarcoma,pancreatic cancer and colorectal cancer cells through YB-1.Furthermore,in 364 cancer cell lines and colorectal adenocarcinoma samples,Pin1 and YB-1 protein levels were significantly posi⁃tively correlated.Immunohistochemical staining analysis demonstrated a significant positive correlation be⁃tween Pin1 and YB-1 protein levels in osteosarcoma,pancreatic adenocarcinoma and colorectal cancer clinical samples.Together,this study highlights an important role for Pin1-YB-1 axis in regulating tumor cell prolif⁃eration.Intervening in the Pin1-YB-1 interaction would serve as an effective therapeutic strategy and provide a potential target for drug design.

关 键 词：脯氨酰异构酶 Y盒结合蛋白1 肿瘤细胞 增殖 正相关 

分 类 号：R730.2[医药卫生—肿瘤]