TPX2 通过 PLK1 促进 OC 中的细胞增殖和迁移。

TPX2 promotes cell proliferation and migration via PLK1 in OC.

机构信息

Clinical Experimental Teaching Center, The First Affiliated Hospital of Xi'an Medical University, Xi'an 710077, Shaanxi, China.

Department of Gynaecology, Shaanxi Provincial People's Hospital, Xi'an 710068, Shaanxi, China.

出版信息

Cancer Biomark. 2018;22(3):443-451. doi: 10.3233/CBM-171056.

DOI:10.3233/CBM-171056

PMID:29865033

Abstract

BACKGROUND

Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated proteinrequired for mitosis and spindle assembly. It has been revealed that TPX2 is overexpressedin various human cancers and promotes cancer progression.

METHODS

The expression of TPX2 was examined in ovarian cancer (OC) tissues and by Western blotting, quantitative real-time reverse transcription PCR (qRT-PCR) and immunohistochemistry. The effects of TPX2 on proliferation and migration of two OC cell lines SKOV3and RMG1 were analyzed using the methylthiazol tetrazolium (MTT) assay, flow cytometry and transwell assay. The mechanisms underlying the effects of TPX2 on OC cells were explored by qRT-PCR and Western blot.

RESULTS

In this study, we found that TPX2 was upregulated in OC tissues. We observed knockdown of TPX2 inhibited the expression of Polo-like kinase 1 (PLK1), which has an important role in the regulation of M phase of the cell cycle, and the activity of Cdc2, induced cell arrested at the G2/M phase and decreased proliferation. Moreover, our data revealed that the levels of PLK1, β-catenin, MMP7 and MMP9 were inhibited following TPX2 knockdown, leading to decrease of cell migration. Finally, we showed that the restoration of PLK1 expression attenuated the anti-proliferation and anti-migration effects of TPX2 knockdown in OC cells.

CONCLUSIONS

TPX2 promotes the proliferation and migration of human OC cells by regulating PLK1 expression.

摘要

背景

靶向微管相关蛋白 Xenopus 驱动蛋白样蛋白 2（TPX2）是有丝分裂和纺锤体组装所必需的。已经揭示，TPX2 在各种人类癌症中过表达，并促进癌症进展。

方法

通过 Western blot、定量实时逆转录 PCR（qRT-PCR）和免疫组织化学检查，检测卵巢癌（OC）组织中 TPX2 的表达。通过甲基噻唑四唑（MTT）测定、流式细胞术和 Transwell 测定分析 TPX2 对两种 OC 细胞系 SKOV3 和 RMG1 的增殖和迁移的影响。通过 qRT-PCR 和 Western blot 探索 TPX2 对 OC 细胞影响的机制。

结果

在这项研究中，我们发现 TPX2 在 OC 组织中上调。我们观察到敲低 TPX2 抑制了 Polo 样激酶 1（PLK1）的表达，PLK1 在细胞周期 M 期的调节中起重要作用，并且 Cdc2 的活性诱导细胞停滞在 G2/M 期并减少增殖。此外，我们的数据表明，TPX2 敲低后，PLK1、β-连环蛋白、MMP7 和 MMP9 的水平降低，导致细胞迁移减少。最后，我们表明，PLK1 表达的恢复减弱了 TPX2 敲低对 OC 细胞的抗增殖和抗迁移作用。