【摘要】 【目的】探讨干扰素调节因子5(IFR5)是否通过下调DNA修复酶PARP-1,进而抑制鼻咽癌细胞的侵袭能力。【方法】本研究使用的临床标本是经病理确诊的鼻咽癌患者组织标本46例和正常组织51例。免疫组化检测鼻咽癌组织和正常组织中IRF5和PARP-1的表达。构建IFR5过表达质粒,上调鼻咽癌细胞CNE-2中IFR5表达,荧光定量PCR(QPCR)和免疫印迹确定建立IRF5过表达细胞。上调IRF5表达后,划痕和transwell实验检测细胞侵袭能力的改变,QPCR和免疫印迹检测PARP-1表达量的变化。上调IFR5表达的同时加入PARP-1过表达质粒,观察PARP-1是否可逆转IFR5对侵袭能力的影响。【结果】免疫组化结果表明IRF5在癌组织中的表达量低于正常组织,而PARP-1则相反。QPCR和免疫印迹确定建立IRF5 mRNA和蛋白过表达的细胞株CNE-2/IFR5。细胞划痕实验显示CNE-2/IFR5愈合率较对照组降低(P<0.01),transwell实验表明CNE-2/IFR5细胞穿过基底膜的数目小于对照组(P<0.01),提示上调IFR5可抑制鼻咽癌细胞的侵袭能力。上调IFR5后,PARP-1 mRNA和蛋白的表达量降低(P<0.01);上调IFR5表达的同时过表达PARP-1,可逆转单独上调IRF5对细胞侵袭能力的改变。提示IFR5可通过下调PARP-1进而抑制鼻咽癌癌细胞的侵袭能力。【结论】IFR5可通过下调PARP-1进而抑制鼻咽癌癌细胞的侵袭能力。本研究可能为降低鼻咽癌侵袭能力提供新的靶点。更多还原

【Abstract】 【Objective】To investigate whether IRF5 can inhibit invasion ability of nasopharyngeal carcinoma by reducing PARP-1(poly(ADP-ribose)polymerase-1).【Methods】Forty-six specimens of nasopharyngeal carcinoma and 51 specimens of normal tissue were confirmed by pathologically in this study. The expression of IRF5 and PARP-1 in nasopharyngeal carcinoma tissues and normal tissues was detected by immunohistochemistry. The IFR5 overexpression plasmid was transfected into the nasopharyngeal carcinoma cell line CNE-2,quantitative PCR and immunoblotting was used to value the expression of IRF5 after transfection. The wound healing and transwell assay was used to investigate the invasion ability. The expression of PARP-1 was valued by quantitative PCR and immunoblotting after over-expression of PFR5.【Results】The results showed that the expression of IRF5 in cancer tissues was lower than that in normal tissues,but the PARP-1 expression was opposite. The IRF5 overexpressing cell line CNE-2/IFR5 was established. The healing rate of CNE-2/IFR5 cells was lower than that of the control cells(P<0.01). Transwell experiments revealed that the number of CNE-2/IFR5 cells passing through the basement membrane was smaller than that of the control group(P<0.01),suggesting that up-regulation of IFR5 could inhibit the invasiveness of nasopharyngeal carcinoma cells. Over-expression of IFR5 led to reduced PARP-1 mRNA and protein(P<0.01). Besides,elevation of PARP-1 can prevent IRF5-induced changes of invasion ability.【Conclusion】Therefore,we speculated that IRF5 can inhibit invasion ability of nasopharyngeal carcinoma by reducing the expression of PARP-1. This study provided a new target for inhibiting the invasion ability of nasopharyngeal carcinoma based on IRF5.更多还原