miR-21通过PDCD4调控肝癌细胞的生长和侵袭

MiR-21 regulates the growth and invasion of liver cancer cells through PDCD4

目的探讨miR-21在原发性肝细胞癌(hepatocellular carcinoma,HCC)组织和细胞中的表达及其可能调控的靶基因。方法检测miR-21在HCC组织和细胞系中的表达,使用miR-21抑制剂后,观察HCC细胞活力和侵袭能力的变化;运用生物信息学分析预测miR-21可能的靶基因。应用miR-21抑制剂后,双荧光素酶报告基因系统检测其对靶基因活性的影响。结果HCC组织中miR-21表达水平显著高于癌旁组织(P<0.05);HCC细胞中miR-21的表达水平显著高于肝细胞(P<0.01)。抑制miR-21后,HCC细胞的活力和侵袭能力降低(P<0.01)。抑癌基因程序性死亡因子4(programmed cell death 4,PDCD4)在HCC组织中的表达显著低于癌旁组织(P<0.01),在肝癌细胞中的表达水平显著低于肝细胞(P<0.01)。干扰PDCD4后,肝癌细胞的活力和侵袭能力提高(P<0.05)。双荧光素酶报告基因检测显示,使用miR-21抑制剂后,PDCD4表达上调(P<0.01),肝癌细胞的侵袭和增殖能力降低(P<0.01)。干扰PDCD4后,肝癌细胞的侵袭和增殖能力升高(P<0.001)。结论miR-21可通过PDCD4调控肝癌细胞的生长和侵袭。

Purpose To evaluate the expression of miR-21 in the tissues and cell lines of hepatocellular carcinoma, and to try to find its possible target genes. Methods The expression profile of miR-21 was detected in hepatocellular carcinoma tissues and cell lines. After miR-21 inhibitor was used, the alterations in the vitality and invasion of hepatocellular carcinoma cells were observed. The possible target gene of miR-21 was predicted by bioinformaties analysis. The influence of miR-21 inhibitors on the target gene activity was evaluated by dual lueiferase reporting gene system. Results The expression level of miR-21 was sig- nificantly higher in hepatocellular carcinoma tissues than that in the adjacent ones （P 〈 0. 05 ）. The expression level of miR-21 in hepatoeellular carcinoma ceils was significantly higher than that in the hepatic cells （P 〈 0. 01 ）. After inhibiting miR-21, the viability and invasion ability of hepatocellular carcinoma cells were decreased （P 〈 0. 01 ）. The expression level of programmed cell death 4 （PDCD4） in hepatocellular carcinoma tissues was significantly lower than that in the adjacent tissues （P 〈0. 01）. Its expression level in hepatocellular carcinoma cells was significantly lower than that in the hepatic cells （P 〈 0. 01）. After interfering with PDCD4, the vitality and invasion ability of liver cancer ceils were increased （ P 〈 0. 05 ）. Dual luciferase reporter gene assay indicated that by inhibiting miR-21, the expression level of PDCD4 was up-regulated （ P 〈 0. 01 ）. The vitality and invasion ability of liver cancer cells were reduced （P 〈 0. 001 ）. Conclusion MiR-21 can regulate the growth and invasion of liver cancer cells through targeting PDCD4.