Elevated expression of the nucleoporin Nup88, a constituent of the nuclear pore complex, is seen in various types of malignant tumors, but whether this overexpression contributes to the malignant phenotype has yet to be determined. Here, we investigated the effect of the overexpression of Nup88 on the migration and invasion of cervical cancer HeLa cells. The overexpression of Nup88 promoted a slight but significant increase in both migration and invasion, whereas knockdown of Nup88 by RNA interference suppressed these phenotypes. The observed phenotypes in Nup88-overexpressing HeLa cells were not due to the progression of the epithelial-to-mesenchymal transition or activation of NF-κB, which are known to be important for cell migration and invasion. Instead, we identified an upregulation of matrix metalloproteinase-12 (MMP-12) at both the gene and protein levels in Nup88-overexpressing HeLa cells. Upregulation of MMP-12 protein by the overexpression of Nup88 was also observed in one other cervical cancer cell line and two prostate cancer cell lines but not 293 cells. Treatment with a selective inhibitor against MMP-12 enzymatic activity significantly suppressed the invasive ability of HeLa cells induced by Nup88 overexpression. Taken together, our results suggest that overexpression of Nup88 can stimulate malignant phenotypes including invasive ability, which is promoted by MMP-12 expression.

在各种类型的恶性肿瘤中都可以看到核孔蛋白 Nup88 的表达升高，这是核孔复合物的一种成分，但这种过度表达是否会导致恶性表型仍有待确定。在这里，我们研究了 Nup88 过表达对宫颈癌 HeLa 细胞迁移和侵袭的影响。Nup88 的过表达促进了迁移和侵袭的轻微但显着增加，而通过 RNA 干扰敲低 Nup88 抑制了这些表型。在过表达 Nup88 的 HeLa 细胞中观察到的表型不是由于上皮间质转化的进展或 NF-κB 的激活，已知这对细胞迁移和侵袭很重要。反而，我们在过表达 Nup88 的 HeLa 细胞的基因和蛋白质水平上发现了基质金属蛋白酶 12 (MMP-12) 的上调。在另一种宫颈癌细胞系和两种前列腺癌细胞系中也观察到 Nup88 过表达导致 MMP-12 蛋白上调，但在 293 细胞中没有观察到。用针对 MMP-12 酶活性的选择性抑制剂治疗显着抑制了由 Nup88 过表达诱导的 HeLa 细胞的侵袭能力。总之，我们的结果表明 Nup88 的过表达可以刺激恶性表型，包括 MMP-12 表达促进的侵袭能力。在另一种宫颈癌细胞系和两种前列腺癌细胞系中也观察到 Nup88 过表达导致 MMP-12 蛋白上调，但在 293 细胞中没有观察到。用针对 MMP-12 酶活性的选择性抑制剂治疗显着抑制了由 Nup88 过表达诱导的 HeLa 细胞的侵袭能力。总之，我们的结果表明 Nup88 的过表达可以刺激恶性表型，包括 MMP-12 表达促进的侵袭能力。在另一种宫颈癌细胞系和两种前列腺癌细胞系中也观察到 Nup88 过表达导致 MMP-12 蛋白上调，但在 293 细胞中没有观察到。用针对 MMP-12 酶活性的选择性抑制剂治疗显着抑制了由 Nup88 过表达诱导的 HeLa 细胞的侵袭能力。总之，我们的结果表明 Nup88 的过表达可以刺激恶性表型，包括 MMP-12 表达促进的侵袭能力。