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核孔蛋白 107 促进宫颈癌肿瘤细胞的存活。

Nucleoporin 107 Promotes the Survival of Tumor Cells in Cervical Cancers.

机构信息

Department of Obstetrics and Gynecology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

出版信息

Gynecol Obstet Invest. 2020;85(1):41-52. doi: 10.1159/000502788. Epub 2019 Sep 5.

Abstract

AIMS

Recent studies indicate that in addition to the construction of nuclear pore complex, nucleoporin (NUP)107 is actively involved in the pathogenesis of numerous cancer types, but the role of NUP107 in cervical carcinoma cells remains unknown.

METHODS

We examined the expression of NUP107 in 30 cases of cervical carcinoma using quantitative reverse transcription-polymerase chain reaction and immunoblots. NUP107 stably overexpressing cell line was established to examine the function of NUP107 in cell viability, TUNEL assay, wound healing assay, 5-ethynyl-2'-deoxyuridine incorporation, and oxidative stress.

RESULTS

NUP107 expression was significantly increased in the cervical carcinoma tissues, compared with their corresponding adjacent normal tissues. Overexpression of NUP107 conferred the cervical cancer cells with significant resistance to oxidative insult, but it had no effects on the migration and proliferation. This pro-survival function of NUP107 was associated with the elevated expression of Bcl-2, the activation of Akt signaling, and increased expression of nucleocytoplasmic transport factors. Silencing of NUP107 increased the sensitivity of cervical cancer cells to oxidative challenge, thereby inducing the apoptosis of cervical cancer cells.

CONCLUSION

NUP107 is significantly increased in cervical tissues and confers the cervical cancer cells with resistance to oxidative damage. These results provide an important role for specific NUP in mediating cervical cancer.

摘要

目的

最近的研究表明,核孔复合体的构建除了核孔蛋白(NUP)107 之外,还积极参与了许多癌症类型的发病机制,但 NUP107 在宫颈癌细胞中的作用尚不清楚。

方法

我们使用定量逆转录-聚合酶链反应和免疫印迹法检查了 30 例宫颈癌中 NUP107 的表达。建立了 NUP107 稳定过表达细胞系,以研究 NUP107 在细胞活力、TUNEL 测定、划痕愈合测定、5-乙炔基-2'-脱氧尿苷掺入和氧化应激中的作用。

结果

与相应的相邻正常组织相比,NUP107 在宫颈癌组织中的表达显著增加。NUP107 的过表达赋予宫颈癌细胞对氧化损伤的显著抗性,但对迁移和增殖没有影响。NUP107 的这种促进生存的功能与 Bcl-2 的表达增加、Akt 信号的激活以及核质转运因子的表达增加有关。NUP107 的沉默增加了宫颈癌细胞对氧化应激的敏感性,从而诱导宫颈癌细胞凋亡。

结论

NUP107 在宫颈癌组织中显著增加,并赋予宫颈癌细胞对氧化损伤的抗性。这些结果为特定 NUP 在介导宫颈癌中的作用提供了重要依据。

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