UHRF1在膀胱尿路上皮癌中对HIF1α-VEGF通路的调控作用  

The Regulatory Effect of UHRF1 on HIF1α-VEGF Pathway in Bladder Urothelial Carcinoma

作　　者：周昌东[1] 杨新平[1] 田玉新[1] 孙凯[1] 林洋[1] 张奇夫 ZHOU Chang-dong;YANG Xin-ping;TIAN Yu-xin;SUN Kai;LIN Yang;ZHANG Qi-fu(Department of Urology,Jilin Province Cancer Hospital,Changchun,Jinlin,130012,China)

机构地区：[1]吉林省肿瘤医院泌尿外科,吉林长春130012

出　　处：《现代生物医学进展》2021年第3期443-449,共7页Progress in Modern Biomedicine

基　　金：吉林省直卫生科研专项项目(sczsy201721)。

摘　　要：目的:本文研究旨在探讨UHRF1对膀胱癌早期诊断和预后的价值。方法:本文研究收集26例膀胱癌病人的癌旁组织和癌症组织,同时用人BCa细胞T24细胞作为体外模型。CCK-8分析、TUNEL染色、LDH活性和Caspase 3/8/9蛋白表活性达水平被用于检测UHRF1的作用。qRT-PCR检测、基因芯片和Western blotting被用于检测UHRF1下游通路。结果:与癌旁组织对比,在膀胱尿路上皮癌膜组织中UHRF1表达量显著激活。同时,III-IV膀胱癌患者的膀胱尿路上皮癌膜组的UHRF1表达显著高于I-II膀胱癌患者组。上调UHRF1能够促进膀胱癌细胞增殖和减少LDH活性水平。在UHRF1上调3天和5天时,膀胱癌细胞中Caspase-3/9活性被抑制。UHRF1过表达能够激活VEGF和HIF1αm RNA和蛋白表达。激活HIF1α-VEGF通路抑制UHRF1对膀胱癌细胞增殖的调节作用。结论:UHRF1通过HIF1α-VEGF通路,促进膀胱癌细胞增殖,提示UHRF1可作为预测膀胱癌的分子标志物。Objective: Bladder cancer is one of the most common diagnostic cancers in the world, and it is also the most lethal malignant tumor of urinary system. This study explored the value of uhrf1 in early diagnosis and prognosis of bladder cancer. Methods: In this study, 26 patients with bladder cancer were collected from the adjacent tissues and cancer tissues, and Bladder cancer cells line T24 cells were used as in vitro models. CCK-8 analysis, TUNEL staining, LDH activity and Caspase 3/8/9 protein surface activity levels were used to detect the effects of UHRF1.Qrt-pcr, gene chip and Western blotting were used to detect the downstream UHRF1 pathway.Results: Compared with paracancerous tissues, the expression of uhrf1 was significantly activated in bladder urothelial carcinoma. At the same time, the expression of uhrf1 in bladder urothelial cancer membrane group was significantly higher than that in I-II bladder cancer group. Up regulation of uhrf1 can promote bladder cancer cell proliferation and reduce LDH activity. Caspase-3/9 activity in bladder cancer cells was inhibited after 3 and 5 days of upregulation of uhrf1. Over expression of uhrf1 can activate the expression of VEGF and HIF1α m RNA and protein. Activation of HIF1α-VEGF pathway inhibits the regulation of uhrf1 on the proliferation of bladder cancer cells. Conclusion: Uhrf1 can promote the proliferation of bladder cancer cells through HIF1α-VEGF pathway, suggesting that uhrf1 can be used as a molecular marker to predict bladder cancer.

关 键 词：UHRF1 VEGF HIF1Α 膀胱尿路上皮癌 

分 类 号：R-33[医药卫生] R737.14