敲除ARID2基因对肺癌细胞生物学行为的影响及机制研究

Effect and mechanism of knockout of ARID2 gene on biological behavior of lung cancer cells

目的研究敲除ARID2基因对肺癌细胞生物学行为的影响及可能机制。方法于肺癌细胞A549、H460中敲除ARID2,运用RT-PCR检测细胞ARID2及MMP2/TIMP2通路相关基因表达,MTT、流式细胞术、Tran-Swell法检测敲除ARID2后A549、H460细胞增殖、凋亡、侵袭及迁移能力,免疫印迹检测端粒酶hTERT表达。结果敲除ARID2后,A549、H460增殖、侵袭、迁移能力增强、凋亡能力降低、hTERT表达升高(P<0.05)。敲除ARID2后,MMP-2mRNA与miR-4443表达升高,TIMP2mRNA表达降低(P<0.05)。结论敲除ARID2基因能通过激活MMP2/TIMP2信号通路促进肿瘤细胞侵袭、迁移并抑制凋亡,并通过促进端粒酶活性维持肿瘤细胞稳定增殖。

Objective To study the effect of ARID2 gene knockout on the biological behavior of lung cancer cells and its possible mechanism.Methods ARID2 was knocked out in lung cancer cell A549 and H460,and the expression of ARID2 and MMP2/TIMP2 pathway related genes was detected by RT-PCR.The proliferation,apoptosis,invasion and migration ability of A549 and H460 cells after ARID2 knockout was detected by MTT,flow cytometry and Transwell method,and the expression of telomerase hTERT was detected by Western blotting.Results After ARID2 knockout,the proliferation,invasion and migration ability of A549 and H460 cells was enhanced,the apoptosis ability was decreased,and the expression of hTERT was increased(P<0.05).After ARID2 knockout,the expression of MMP-2 mRNA and miR-4443 was increased,and the expression of TIMP2 mRNA was decreased(P<0.05).Conclusion ARID2 gene knockout can promote the invasion and migration of tumor cells and inhibit apoptosis by activating MMP2/TIMP2 signaling pathway,and maintain the stable proliferation of tumor cells by promoting telomerase activity.