IPI-504通过LINC00312/let-7b-5p/EBF1轴抑制胰腺癌细胞的增殖和迁移  

IPI-504 inhibits proliferation and migration of pancreatic cancer cells via the LINC00312/let-7b-5p/EBF1 axis

作　　者：胡耀元 谭晓冬[1] 李锐 HU Yaoyuan;TAN Xiaodong;LI Rui(Department of General Surgery,Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院普通外科,沈阳110004

出　　处：《中国医科大学学报》2022年第11期1014-1020,共7页Journal of China Medical University

基　　金：辽宁省重点研发计划(2020JH6/10500055)。

摘　　要：目的探讨IPI-504诱导的LINC00312对胰腺癌细胞增殖、迁移和上皮-间质转化的抑制作用,并阐明其作用机制。方法通过生物信息学分析预测let-7b-5p与LINC00312、EBF1 mRNA的潜在结合位点,应用双荧光素酶报告基因实验验证靶向关系。将PANC-1细胞分为对照组、IPI-504组、IPI-504+敲减对照组、IPI-504+敲减LINC00312组、IPI-504+NC mimics组、IPI-504+let-7b-5p mimics组和IPI-504+敲减EBF1组,实时荧光定量PCR检测细胞LINC00312和let-7b-5p的表达,CCK-8法检测细胞增殖活性,Transwell检测细胞迁移能力,Western blotting检测细胞EBF1蛋白表达。结果let-7b-5p与LINC00312、EBF1 mRNA结合,敲减LINC00312、转染let-7b-5p模拟物和敲减EBF1均降低经IPI-504处理的PANC-1细胞中EBF1蛋白表达,促进细胞增殖和迁移。结论IPI-504上调胰腺癌细胞LINC00312表达,LINC00312通过海绵化let-7b-5p上调EBF1表达,从而抑制胰腺癌细胞的增殖和迁移。Objective To explore the mechanism and inhibitory effect of IPI-504-induced LINC00312 on the proliferation,migration,and epithelial-mesenchymal transition of pancreatic cancer cells.Methods The potential binding sites of let-7b-5p to LINC00312 and EBF1 mRNA were predicted using bioinformatics,and the targeting relationship was verified using dual-luciferase reporter gene experiments.PANC-1 cells were divided into control,IPI-504,IPI-504+knockdown control,IPI-504+LINC00312 knockdown,IPI-504+NC mimics,IPI-504+let-7b-5p mimics,and IPI-504+EBF1 knockdown groups.The expressions of LINC00312 and let-7b-5p were detected using real-time fluorescence quantitative PCR,the proliferation activity of cells was detected using CCK-8 assay,the migration ability of cells was detected using Transwell assay,and the expression of EBF1 protein was detected using Western blotting.Results let-7b-5p binded to LINC00312 and EBF1 mRNA.Knockdown of LINC00312,transfection of let-7b-5p mimics,and knockdown of EBF1 reduced EBF1 protein expression and promoted cell proliferation and migration in IPI-504-treated PANC-1 cells.Conclusion IPI-504 upregulates the expression of LINC00312 in pancreatic cancer cells.LINC00312 up-regulates the expression of EBF1 by sponging let-7b-5p,thus inhibiting the proliferation and migration of pancreatic cancer cells.

关 键 词：IPI-504 胰腺癌 LINC00312 let-7b-5p EBF1 

分 类 号：R730.53[医药卫生—肿瘤]