Downregulation of SPINK13 Promotes Metastasis by Regulating uPA in Ovarian Cancer Cells

被引：18

作者：

Cai, Shengyun ^{[1
]}

Zhang, Pei ^{[2
]}

Dong, Suhe ^{[2
]}

Li, Li ^{[1
]}

Cai, Jianming ^{[2
]}

Xu, Mingjuan ^{[1
]}

机构：

[1] Second Mil Med Univ, Changhai Hosp, Dept Gynaecol & Obstet, Shanghai, Peoples R China

[2] Second Mil Med Univ, Fac Naval Med, Dept Radiat Med, Xiangyin Rd, Shanghai, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2018年 / 45卷 / 03期

基金：

美国国家科学基金会;

关键词：

Ovarian cancer; SPINK13; Metastasis; uPA; EPITHELIAL-MESENCHYMAL TRANSITIONS; SERINE-PROTEASE INHIBITOR; PLASMINOGEN-ACTIVATOR; E-CADHERIN; GENE; KAZAL; FAMILY; SYSTEM; STATISTICS; MUTATIONS;

D O I：

10.1159/000487348

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background/Aims: Ovarian cancer (OC) is the fifth leading cause of cancer-related death in women, and it is difficult to diagnose at an early stage. The purpose of this study was to explore the prognostic biological markers of OC. Methods: Univariate Cox regression analysis was used to identify genes related to OC prognosis from the Cancer Genome Atlas(TCGA) database. Immunohistochemistry was used to analyse the level of SPINK13 in OC and normal tissues. Cell proliferation, apoptosis and invasion were performed using MTT assay, flow cytometric analysis and Transwell assay, respectively. Results: We identified the Kazal-type serine protease inhibitor-13 (SPINK13) gene related to OC prognosis from the Cancer Genome Atlas (TCGA) database by univariate Cox regression analysis. Overexpression of SPINK13 was associated with higher overall survival rate in OC patients. Immunohistochemistry showed that the level of SPINK13 protein was significantly lower in OC tissues than in normal tissues (P < 0.05). In vitro experiments showed that the overexpression of SPINK13 inhibited cellular proliferation and promoted apoptosis. Moreover, SPINK13 inhibited cell migration and epithelial to mesenchymal transition (EMT). SPINK13 was found to inhibit the expression of urokinase-type plasminogen activator (uPA), while recombinant uPA protein could reverse the inhibitory effect of SPINK13 on OC metastasis. Conclusion: These results indicate that SPINK13 functions as a tumour suppressor. The role of SPINK13 in cellular proliferation, apoptosis and migration is uPA dependent, and SPINK13 may be used as a potential biomarker for diagnosis and targeted therapy in OC. (c) 2018 The Author(s) Published by S. Karger AG, Basel

引用

页码：1061 / 1071

页数：11

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