甘草酸通过调控miR-142/ZEB1 分子轴影响非小细胞肺癌HCC827 和A549 细胞的恶性生物学行为

目的：探讨甘草酸（GA）通过调控miR-142/锌指E 盒结合的同源盒蛋白1（ZEB1）分子轴对非小细胞肺癌（NSCLC）HCC827 和A549 细胞增殖、侵袭和迁移的影响。方法：HCC827 和A549 细胞培养和转染完成后，分成4 组：NC组（未经转染+3mmol/L GA）、miR-142 inhibitor 组（敲降miR-142+3 mmol/L GA）、pcDNA3.1-ZEB1 组（过表达ZEB1+3 mmol/L GA）和pcDNA3.1-ZEB1+miR-142 mimic 组（过表达ZEB1 及miR-142+3 mmol/L GA）。采用qPCR检测不同浓度GA处理后HCC827 和A549 细胞中miR-142 的表达水平，WB实验检测HCC827 和A549 细胞中ZEB1 蛋白的表达水平，采用MTT和Transwell 检测HCC827 和A549细胞的增殖、侵袭和迁移能力，采用双荧光素酶报告基因检测miR-142 与ZEB1 的靶向关系。结果：GA显著抑制HCC827 和A549 细胞的增殖、侵袭和迁移，且显著上调miR-142 的表达水平（P<0.05 或P<0.01）；miR-142 通过靶向结合ZEB1 的3''-UTR 区域下调ZEB1 的表达水平（P<0.05 或P<0.01）；进一步实验证实，GA通过上调miR-142 抑制ZEB1 的表达水平，进而抑制HCC827 和A549 细胞增殖、侵袭和迁移（P<0.05 或P<0.01）。结论：GA能够抑制NSCLC HCC827 和A549 细胞增殖、侵袭和迁移，其机制为GA通过上调miR-142对ZEB1 的抑制作用，从而抑制HCC827和A549 细胞的恶性生物学行为。

Glycyrrhizin affects malignant biological behaviors of non-small cell lung cancer HCC827 and A549 cells via regulating miR-142/ZEB1 axis

Objective: To explore the effect of glycyrrhizin (GA) on the proliferation, invasion and migration of non-small cell lung cancer HCC827 and A549 cells via regulating miR-142/ZEB1 (Zinc finger E-box-binding homeobox 1) axis. Methods: After being cultured and transfected, HCC827 and A549 cells were divided into 4 groups: NC group (untransfected+3 mmol/L GA), miR-142 inhibitor group (miR-142 knockdown+3 mmol/L GA), pcDNA3.1-ZEB1 group (ZEB1 over-expression+3 mmol/L GA) and pcDNA3.1-ZEB1+miR-142 mimic group (ZEB1 over-expression+miR-142+3 mmol/L GA). qPCR was used to detect the expression level of miR-142 in HCC827 and A549 cells treated with different concentrations of GA. MTT and Transwell assays were used to examine the proliferation,invasion and migration of HCC827 and A549 cells. WB was used to detect the expression level of ZEB1 protein in HCC827 and A549 cells. Dual-luciferase reporter gene assay was used to explore the relationship between miR-142 and ZEB1. Results: GA significantly inhibited the proliferation, invasion and migration of HCC827 and A549 cells, and up-regulated the expression level of miR-142 (P<0.05 or P<0.01). Dual-luciferase reporter gene assay showed that miR-142 could targetedly combine with 3''-UTR of ZEB1 and downregulate the expression of ZEB1 (P<0.05 or P<0.01). Further experiment validated that GA inhibited ZEB1 expression via up-regulating miR-142, thus suppressed proliferation, invasion and migration of HCC827 and A549 cells (P<0.05 or P<0.01). Conclusion: GA inhibits the proliferation, invasion and migration of NSCLC HCC827 and A549 cells, the mechanism of which is that GA inhibits the malignant biological behavior of NSCLC HCC827 and A549 cells via up-regulating the inhibition effect of miR-142 on ZEB1.