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靶向二肽基肽酶 8 基因通过抑制细胞周期蛋白 D1 和 MMP2MMP9 信号通路抑制宫颈癌的增殖、迁移和侵袭。

Targeting dipeptidyl peptidase 8 genes inhibits proliferation, migration and invasion by inhibition of cyclin D1 and MMP2MMP9 signal pathway in cervical cancer.

机构信息

Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.

出版信息

J Gene Med. 2018 Dec;20(12):e3056. doi: 10.1002/jgm.3056. Epub 2018 Nov 8.

DOI:10.1002/jgm.3056
PMID:30225951
Abstract

BACKGROUND

DPP8 is a member of the dipeptidyl peptidase IV family, which belongs to the S9b protease subfamily. It regulates cell proliferation, apoptosis, migration and invasion during cancer progression.

METHODS

To investigate the role of DPP8 in cervical cancer, we examined DPP8 levels in cervical cancer tissues and cells. The localization of DPP8 was determined by immunofluorescence staining. Subsequently, SiHa and HeLa cells were treated with small interfering RNA (siRNA)-DPP8. We used cell cycle analysis, an 5-ethyl-2'-deoxyuridine assay proliferation assay and a cellular apoptosis assay to determine the effect of DPP8 on the proliferation and apoptosis of cervical cancer cells. We used a Transwell assay to assess the number of transfection cancer cells migrating through the matrix. A real-time polymerase chain reaction and western blot analysis were used to analyze the expression of related proteins and to determine the phenotype caused by the depletion or overexpression of DPP8 in cervical cancer cells.

RESULTS

We observed that DPP8 was highly expressed in cervical cancer tissues and cells. DPP8 expression was observed in the cytosol and in the perinuclear area, as well as in the nuclei of cervical cancer cells. Notably, when cells were treated with siRNA-DPP8, the expression of BAX increased, and the expression of cyclin D1, Bcl-2, MMP2 and MMP9 was downregulated. In cervical cancer cell lines, silencing the expression of DPP8 not only suppressed the proliferation, migration and invasion of the cervical cancer cells, but also promoted cervical cancer cell apoptosis.

CONCLUSIONS

The data obtained in the present study reveal that DPP8 promotes the progression of cervical cancer.

摘要

背景

DPP8 是二肽基肽酶 IV 家族的成员,属于 S9b 蛋白酶亚家族。它在癌症进展过程中调节细胞增殖、凋亡、迁移和侵袭。

方法

为了研究 DPP8 在宫颈癌中的作用,我们检测了宫颈癌组织和细胞中的 DPP8 水平。通过免疫荧光染色确定 DPP8 的定位。随后,用小干扰 RNA(siRNA)-DPP8 处理 SiHa 和 HeLa 细胞。我们使用细胞周期分析、5-乙基-2'-脱氧尿苷测定增殖试验和细胞凋亡试验来确定 DPP8 对宫颈癌细胞增殖和凋亡的影响。我们使用 Transwell assay 评估穿过基质的转染癌细胞的数量。实时聚合酶链反应和 Western blot 分析用于分析相关蛋白的表达,并确定 DPP8 在宫颈癌细胞中的耗竭或过表达引起的表型。

结果

我们观察到 DPP8 在宫颈癌组织和细胞中高度表达。DPP8 表达可见于细胞质和核周区,以及宫颈癌细胞的核内。值得注意的是,当用 siRNA-DPP8 处理细胞时,BAX 的表达增加,而 cyclin D1、Bcl-2、MMP2 和 MMP9 的表达下调。在宫颈癌细胞系中,沉默 DPP8 的表达不仅抑制了宫颈癌细胞的增殖、迁移和侵袭,还促进了宫颈癌细胞凋亡。

结论

本研究的数据表明 DPP8 促进了宫颈癌的进展。

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