目的：探讨miR-192-5p靶向E盒锌指结合同源框2（ZEB2）对胰腺癌PANC-1细胞增殖、迁移、侵袭和上皮间质转化（EMT）的影响及其作用机制。方法：利用TCGA数据库数据分析miR-192-5p和ZEB2在胰腺癌组织中的表达及两者的相关性。采用qPCR法和WB法分别检测人正常胰腺上皮细胞HPNE和胰腺癌PANC-1细胞中miR-192-5p和ZEB2的表达水平。利用脂质体转染技术转染PANC-1细胞，实验分为miR-192-5p mimic组、Mimic NC组、miR-192-5p inhibitor组、Inhibitor NC组、Mimic NC+pcDNA3.1 组 、miR-192-5p mimic+pcDNA3.1 组 、miR-192-5p mimic+pcDNA3.1-ZEB2 组。CCK-8 法 、克隆形成 、划痕愈合 、Transwell实验分别检测转染PANC-1细胞的增殖、克隆形成、迁移和侵袭能力。qPCR法、WB法、双重免疫荧光实验检测PANC-1细胞中ZEB2、E-cadherin、vimentin的表达水平。通过生物信息学网站预测miR-192-5p的靶基因，并利用双荧光素酶报告基因实验验证miR-192-5p对靶基因的调控作用。结果：胰腺癌组织中ZEB2的表达显著高于正常胰腺组织（P<0.01），且胰腺癌组织中miR-192-5p和ZEB2表达呈负相关（r=-0.419，P<0.01）。与HPNE细胞比较，PANC-1细胞中miR-192-5p低表达、ZEB2蛋白高表达（均P<0.01）。miR-192-5p过表达后，PANC-1细胞增殖、克隆形成、迁移和侵袭能力均显著降低，E-cadherin的mRNA和蛋白表达均上调、vimentin和ZEB2 mRNA和蛋白表达均下调；而抑制miR-192-5p后得到了相反的结果（P<0.05或P<0.01）。miR-192-5p靶向调控ZEB2的表达，过表达ZEB2可部分逆转上调miR-192-5p对PANC-1细胞增殖、迁移、侵袭和EMT进程的抑制作用。结论：miR-192-5p通过靶向ZEB2调控胰腺癌PANC-1细胞的恶性生物学行为。

Objective: To investigate the effect and mechanism of miR-192-5p targeting ZEB2 (zinc finger E-box binding homeobox 2)on the proliferation, migration, invasion and EMT (epithelial-mesenchymal transition) of pancreatic cancer PANC-1 cells. Methods:The TCGA database was used to analyze the expression of miR-192-5p and ZEB2 as well as their correlation in pancreatic cancer tissue.The expression levels of miR-192-5p and ZEB2 were detected by qPCR and WB in human normal pancreatic epithelial HPNE cells and pancreatic cancer PANC-1 cells. PANC-1 cells were transfected with liposome, and divided into miR-192-5p mimic group, Mimic NC group, miR-192-5p inhibitor group, Inhibitor NC group, Mimic NC+pcDNA3.1 group, miR-192-5p mimic+pcDNA3.1 group, andmiR-192-5p mimic+pcDNA3.1-ZEB2 group. The proliferation, colony formation, migration and invasion abilities of transfected PANC-1 cells were detected by CCK-8, colony formation, scratch healing and Transwell experiments, respectively. The expression of ZEB2,E-cadherin and vimentin was detected by qPCR, WB method and double immunofluorescence assay. Bioinformatics was used to predict the target gene of miR-192-5p, and the regulatory effect of miR-192-5p on the target gene was verified by dual luciferase report gene experiment. Results: The expression of ZEB2 in pancreatic cancer tissue was significantly higher than that in normal pancreatic tissue (P<0.01), and the expression of miR-192-5p and ZEB2 in pancreatic cancer tissue was inversely correlated (r=-0.419, P<0.01).Compared with normal pancreatic epithelial HPNE cells, the expression level of miR-192-5p was significantly lower while the expression level of ZEB2 protein was higher in pancreatic cancer PANC-1 cells (all P<0.01). Overexpression of miR-192-5p significantly reduced the proliferation, colony formation, migration and invasion ability of PANC-1 cells, upregulated the mRNA and protein expression of E-cadherin, and downregulated the mRNA and protein expression of vimentin and ZEB2, while inhibition of miR-192-5p achieved the opposite results (P<0.05 or P<0.01). miR-192-5p targetedly regulated the expression of ZEB2, and overexpression of ZEB2 could reverse the inhibitory effects of miR-192-5p overexpression on the proliferation, colony formation,migration, invasion and EMT of PANC-1 cells. Conclusion: miR-192-5p regulates the malignant biological behaviors of pancreatic cancer PANC-1 cells by targeting ZEB2.

河北省自然科学基金资助项目（No.H2021209026）；河北省省级科技计划资助项目（No.213777115D）；河北省人力资源和社会保障 厅科研资助项目（No.C20210340）