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。

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

胡耀元, 谭晓冬, 李锐

中国医科大学附属盛京医院普通外科, 沈阳 110004

收稿日期:2022-05-15发布日期:2022-11-09
通讯作者:李锐E-mail:lirui@cmu.edu.cn
作者简介:胡耀元（1993-），男，医师，硕士.
基金资助:辽宁省重点研发计划（2020JH6/10500055）


关键词: IPI-504, 胰腺癌, LINC00312, let-7b-5p, EBF1
Abstract: 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.
Key words: IPI-504, pancreatic cancer, LINC00312, let-7b-5p, EBF1
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