摘要目的:探讨长链非编码核糖核酸ZNRD1-AS1(lncRNA ZNRD1-AS1)在胃癌多药耐药(MDR)中的作用及机制。方法:采用24孔板体外培养胃癌MGC-803细胞株，设空白对照组、MDR组、空载质粒组、lncRNA ZNRD1-AS1过表达组、微小核糖核酸-375模拟物(miR-375 mimic)组及联合干预组。除空白对照组以外，均采用阿霉素梯度浓度法建立MDR株。建立成功以后，lncRNA ZNRD1-AS1过表达组和miR-375 mimic组分别采用慢病毒转染法转染lncRNA ZNRD1-AS1过表达质粒和miR-375 mimic，空载质粒组转染空载质粒与模拟物对照(mimic NC)。共培养48 h，采用荧光定量聚合酶链反应(qPCR)检测lncRNA ZNRD1-AS1和miR-375表达，采用蛋白质印迹法(Western blot)实验检测Yes相关蛋白1(YAP1)、哺乳动物不育系20样激酶1(Mst1)、大肿瘤抑制基因-1(Lats1)的蛋白表达，采用噻唑蓝(MTT)实验和流式细胞实验检测细胞的增殖活力与凋亡率，Transwell实验检测MGC-803细胞侵袭能力。结果:各组之间的lncRNA ZNRD1-AS1、miR-375、YAP1表达水平差异均有统计学意义( F＝60.465、75.695、63.441，均 P<0.05)；细胞增殖活力、凋亡率与侵袭数目差异也有统计学意义( F＝ 26.818、63.854、16.323，均 P<0.05)。MDR组lncRNA ZNRD1-AS1和YAP1表达水平分别为1.736±0.084和0.825±0.135，高于对照组(1.025±0.036和0.155±0.02)，miR-375表达为0.054±0.018，低于对照组(0.128±0.028)；细胞增殖活力和迁移数目分别为0.855±0.026和152.5±20.5，高于对照组(0.652±0.015和85.0±15.5)，凋亡率为(3.85±1.02)%，低于对照组[(6.55±1.05)%， P<0.05]。lncRNA ZNRD1-AS1过表达组lncRNA ZNRD1-AS1和YAP1表达水平分别为6.582±1.035和1.256±0.185，均高于MDR组，miR-375表达水平为0.015±0.011，低于MDR组；细胞增殖活力和迁移数目分别为0.987±0.030和(202.5±32.5)个，高于MDR组，凋亡率为(2.03±0.62)%，低于MDRMDR组( P<0.05)。miR-375 mimic组lncRNA ZNRD1-AS1和YAP1表达水平分别为0.225±0.086和0.056±0.035，均低于MDR组，miR-375表达水平为32.524±5.254，高于MDR组；细胞增殖活力和迁移能力为0.562±0.085和(80.5±14.6)个，低于MDR组，凋亡率为(18.25±2.10)%，高于MDR组( P<0.05)。共干预组各个指标的变化水平介于lncRNA ZNRD1-AS1过表达组与miR-375 mimic组之间，与两组比较差异有统计学意义( P<0.05)。 结论:lncRNA ZNRD1-AS1能够通过miR-375调节胃癌细胞的行为学特征，从而促进MDR，其机制可能与YAP1介导的Hippo信号通路有关。

abstractsObjective:To analyze the role and mechanism of long noncoding ribonucleic acid ZNRD1-AS1 (lncRNA ZNRD1-AS1) in multidrug resistance (MDR) of gastric cancer, so as to provide new ideas for diagnosis and treatment targets.Methods:MGC-803 cells were cultured in 24-well plates divided into blank control group, MDR group, empty plasmid group, lncRNA ZNRD1-AS1 overexpression group, micro ribonucleic acid (miR)-375 mimic group and combined intervention group. Multidrug resistant strains were established by gradient concentration method of doxorubicin except for blank control group. After successful establishment, lncRNA ZNRD1-AS1 overexpression plasmid and micro ribonucleic acid-375 mimic (miR-375 mimic) were transfected by lentivirus transfection in lncRNA ZNRD1-AS1 overexpression plasmid and miR-375 mimic group, respectively. The null plasmid group was transfected with null plasmid and mimic NC. After 48 h of co-culture, the expressions of lncRNA ZNRD1-AS1 and miR-375 were determined by fluorescence quantitative PCR assay, the protein expressions of Yes-associated protein 1 (YAP1), Mst1 and Lats1 were determined by Western blotting assay, and the proliferation activity and apoptosis rate of the cells were determined by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry assay. Transwell assay was used to determine the invasion ability of MGC-803 cells.Results:There were significant differences in expression levels of lncRNA ZNRD1-AS1, miR-375 and YAP1 among groups ( F=60.465, 75.695 and 63.441, all P<0.05), and there were also significant differences in cell proliferation activity, apoptosis rate and invasion number among groups ( F= 26.818, 63.854, 16.323, all P<0.05). The expression levels of lncRNA ZNRD1-AS1 and YAP1 in multi-drug resistance group were 1.736±0.084 and 0.825±0.135, which were higher than those (1.025±0.036 and 0.155±0.02) of the control group, and the expression of miR-375 in multi-drug resistance group was 0.054±0.018, which was lower than that (0.098±0.028) of the control group; The number of cell proliferation ability and migration counts in multi-drug resistance group were 0.855±0.026 and 152.5±20.5, which were higher than those (0.652±0.015 and 85.0±15.5) of the control group, and the apoptosis rate in multi-drug resistance group was (3.85±1.02)%, which was lower than that [(6.55±1.05)%] of the control group ( P<0.05). The expression levels of lncRNA ZNRD1-AS1 and YAP1 in lncRNA ZNRD1-AS1 overexpression group were 6.582±1.035 and 1.256±0.185, which were higher than those in multi-drug resistance group, and the expression level of miR-375 in lncRNA ZNRD1-AS1 overexpression group was 0.015±0.011, which was lower than that of multi-drug resistance group; The cell proliferation activity and migration number were 0.987±0.030 and (202.5±32.5) cells in lncRNA ZNRD1-AS1 overexpression group, which were higher than those in MDR group, and the apoptosis rate in lncRNA ZNRD1-AS1 overexpression group was (2.03±0.62)%, which was lower than that in MDR group ( P<0.05). The expression levels of lncRNA ZNRD1-AS1 and YAP1 in miR-375 mimic group were 0.225±0.086 and 0.056±0.035, which were lower than those of multi-drug resistance group, and the expression level of miR-375 in miR-375 mimic group was 32.524±5.254, which was higher than that of multi-drug resistance group; The cell proliferation activity and migration ability were 0.562±0.085 and (80.5±14.6) cells in miR-375 mimic group, which were lower than those of MDR group, and the apoptosis rate in miR-375 mimic group was (18.25±2.10)%, which was higher than that of MDR group ( P<0.05). The change levels of each index in the co-intervention group were between those of lncRNA ZNRD1-AS1 overexpression group and miR-375 mimic group, and the difference between groups was statistically significant too ( P<0.05). Conclusion:LncRNA ZNRD1-AS1 could regulate the behavioral characteristics of gastric cancer cells through miR-375, thereby promoting MDR, and its mechanism may be related to YAP1-mediated Hippo signaling pathway.