MicroRNA-425-5p通过靶向Fas信号通路调控肺癌A549细胞增殖、凋亡和转移的机制研究  

MicroRNA-425-5p regulates proliferation,apoptosis and metastasis of lung cancer A549 cells by targeting Fas-related signaling pathways

作　　者：李淑勤 赵树强[2] 郑丽琴[2] 任来峰 LI Shuqin;ZHAO Shuqiang;ZHENG Liqin;REN Laifeng(Department of Internal Medicine,Department of Clinical Medicine,Fenyang College,Shanxi Medical University,Lvliang 032200,China)

机构地区：[1]山西医科大学汾阳学院临床医学系内科教研室,吕梁032200 [2]山西医科大学附属汾阳医院,吕梁032200 [3]山西省肿瘤医院,太原030003

出　　处：《中国免疫学杂志》2022年第4期437-442,共6页Chinese Journal of Immunology

摘　　要：目的:探究miR-425-5p通过靶向Fas相关信号通路调控肺癌A549细胞增殖、凋亡和转移的机制。方法:利用TCGA数据库分析miR-425-5p和Fas的相关性,双荧光素酶报告验证miR-425-5p与Fas的靶向关系。将A549细胞分为NC组、inhibitor组、inhibitor+si-Fas组和si-Fas组,检测各组中miR-425-5p、Fas mRNA和蛋白、TNF-α和可溶性白细胞介素-2受体(sIL-2R)的水平以及各组细胞增殖、迁移、侵袭、凋亡的能力。结果:在TCGA数据库的512例肺腺癌患者中miR-425-5p和Fas呈负相关(P<0.001)。过表达miR-425-5p可以通过靶向结合Fas mRNA抑制Fas蛋白的表达(P<0.05)。inhibitor组的Fas mRNA和蛋白显著高于NC组(P<0.05),inhibitor+si-Fas组的Fas mRNA和蛋白水平显著低于inhibitor组(P<0.05)。与NC组比较,inhibitor组细胞的增殖、迁移、侵袭能力以及TNF-α和sIL-2R表达水平升高而凋亡率降低(P<0.05)。inhibitor+si-Fas组的增殖、迁移、侵袭能力以及TNF-α和sIL-2R表达显著高于inhibitor组而凋亡率低于inhibitor组(P<0.05)。结论:细胞实验发现miR-425-5p可靶向结合并抑制Fas的表达。miR-425-5p可以通过靶向抑制Fas的表达抑制肺癌细胞凋亡并促进细胞增殖、转移和免疫抑制能力,从而发挥促癌作用。Objective:To explore the mechanism of microRNA(miR)-425-5 p regulates the proliferation,apoptosis and metastasis of lung cancer A549 cells by targeting Fas-related signaling pathways.Methods:The TCGA database was used to analyze the correlation between miR-425-5 p and Fas. The targeting relationship between miR-425-5 p and Fas was verified by dual luciferase report. A549 cells were divided into NC group,inhibitor group,inhibitor+si-Fas group and si-Fas group. The levels of miR-425-5 p,Fas mRNA and protein,tumor necrosis factor-α(TNF-α)and soluble interleukin-2 receptor(sIL-2 R)in each group,and the proliferation,migration,invasion and apoptosis were measured.Results:Among the 512 lung adenocarcinoma patients in the TCGA database,miR-425-5 p was negatively correlated with Fas(P<0.001). Overexpression of miR-425-5 p inhibited the expression of Fas protein by targeting Fas mRNA(P<0.05). Fas mRNA and protein in inhibitor group were significantly higher than those in the NC group(P<0.05). Fas mRNA and protein levels in the inhibitor+si-Fas group were significantly lower than those in the inhibitor group(P<0.05).Compared with the NC group,the cell proliferation,migration,invasion ability and the expression levels of TNF-α and sIL-2 R in the inhibitor group increased,while the apoptosis rate was decreased(P<0.05). The proliferation,migration,invasion ability and the expression of TNF-α and sIL-2 R in the inhibitor+si-Fas group were significantly higher than those in the inhibitor group,and the apoptosis rate was lower than that in the inhibitor group(P<0.05).Conclusion:miR-425-5 p can target and inhibit the expression of Fas through cell experiments. miR-425-5 p can inhibit lung cancer cell apoptosis and promote cell proliferation,metastasis and immunosuppression by targeting the expression of Fas,thereby exerting a cancer-promoting effect.

关 键 词：肺癌 microRNA-425-5p FAS 免疫抑制 

分 类 号：R734.2[医药卫生—肿瘤]