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Gfi-1通过靶向FBW7泛素连接酶表达促进人宫颈癌的增殖。

Gfi-1 promotes proliferation of human cervical carcinoma via targeting of FBW7 ubiquitin ligase expression.

作者信息

Cai Hongbing, Zhang Fan, Li Zhen

机构信息

Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University,

Hubei Clinical Cancer Study Center,

出版信息

Cancer Manag Res. 2018 Aug 23;10:2849-2857. doi: 10.2147/CMAR.S161130. eCollection 2018.

Abstract

BACKGROUND

The independent growth factor 1 (Gfi-1) is a transcription factor essential for several diverse hematopoietic functions and developments. However, the role and molecular mechanism of Gfi-1 in the development and progression of cervical cancer remains unclear.

PURPOSE

The present study investigates the relation of expression of Gfi-1 with prognoses in patients with cervical cancer.

METHODS

We used Western blot and reverse transcription polymerase chain reaction (RT-PCR) and the inhibition of proliferation and metastasis of cervical cancer cells in vitro.

RESULTS

This study confirms that the expression of Gfi-1 in cervical cancer tissues was higher than that in adjacent normal tissues. The level of Gfi-1 mRNA in human cervical cancer tissues was significantly higher than that in normal tissues adjacent to cancer. Furthermore, overexpression of Gfi-1 promoted cell proliferation, colony formation, and migration of cervical cancer cells. The increased expression of Gfi-1 promotes the proliferation of cervical cancer cells targeting the tumor suppressor F-box and WD repeat domain containing 7 (FBW7). Clinically, our data suggest that overexpression of Gfi-1 is associated with poor prognosis in patients with cervical cancer. In a tumor xenograft model, knockdown of Gfi-1 inhibited the tumor growth of Hela cells in vivo.

CONCLUSION

Our results reveal that Gfi-1 plays an important role in cervical cancer and Gfi-1/FBW7 axis serves as a potential therapeutic target for cervical cancer.

摘要

背景

独立生长因子1(Gfi-1)是一种对多种不同造血功能和发育至关重要的转录因子。然而,Gfi-1在宫颈癌发生发展中的作用及分子机制仍不清楚。

目的

本研究探讨Gfi-1表达与宫颈癌患者预后的关系。

方法

我们采用蛋白质免疫印迹法和逆转录聚合酶链反应(RT-PCR)以及体外抑制宫颈癌细胞的增殖和转移。

结果

本研究证实,Gfi-1在宫颈癌组织中的表达高于相邻正常组织。人宫颈癌组织中Gfi-1 mRNA水平显著高于癌旁正常组织。此外,Gfi-1的过表达促进宫颈癌细胞的增殖、集落形成和迁移。Gfi-1表达增加通过靶向肿瘤抑制因子含F盒和WD重复结构域7(FBW7)促进宫颈癌细胞增殖。临床上,我们的数据表明Gfi-1过表达与宫颈癌患者预后不良相关。在肿瘤异种移植模型中,敲低Gfi-1可抑制体内Hela细胞的肿瘤生长。

结论

我们的结果表明,Gfi-1在宫颈癌中起重要作用,Gfi-1/FBW7轴可作为宫颈癌的潜在治疗靶点。

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