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Oncogenic Role of NUPR1 in Ovarian Cancer
- Source :
- OncoTargets and Therapy. 13:12289-12300
- Publication Year :
- 2020
- Publisher :
- Informa UK Limited, 2020.
-
Abstract
- Background Nuclear protein 1 (NUPR1) plays a critical role in the development and progression of various types of human cancers. However, the role and mechanism of NUPR1 in ovarian cancer have not been elucidated. The purpose of this study was to investigate the effect of NUPR1 on ovarian cancer in vivo and in vitro. Materials and Methods Through the pretreatment of ovarian cancer cell lines, including A2780 and SKOV3 cells, the expression of NUPR1 was detected by RT-PCR and Western blot assays. When NUPR1 was overexpressed and knocked down in A2780 cells and overexpressed in SKOV3 cells, the MTT assays, colony formation assays and EdU assays were used to detect cell proliferation. Furthermore, cell invasion and migration ability were detected with the transwell assays. Cell cycle and apoptosis of A2780 cells after small interfering RNA-NUPR1 (siRNA-NUPR1) were detected by flow cytometry assays. Finally, the effect of NUPR1 gene silencing on the growth of ovarian cancer was evaluated by tumor xenograft experiment in vivo. Results The expression of NUPR1 protein in A2780 cells was significantly higher than that in ovarian surface epithelium (OSE) cells (P < 0.05). The results showed that downregulation of NUPR1 gene expression significantly inhibited the proliferation, migration and invasion ability of A2780 cells, and increased apoptosis of A2780 cells, which expressed relatively high levels of NUPR1. And the expression of apoptosis-related proteins caspase 3, caspase 9 and Bax was upregulated when NUPR1 was knocked out, while the expression of anti-apoptotic proteins of Bcl-2 and Bcl-xl was downregulated. At the same time, the opposite results were observed when NUPR1 was overexpressed in A2780 and SKOV3 cells. Notably, the effect of NUPR1 overexpression in A2780 cells could be partially or completely eliminated by treatment with the AKT inhibitor LY294002. In addition, NUPR1 knockdown could effectively inhibit tumor growth of mice in vivo. Conclusion In summary, NUPR1 has a carcinogenic effect in ovarian cancer, and the oncogenic effect of NUPR1 in ovarian cancer may be achieved by the AKT pathway.
- Subjects :
- 0301 basic medicine
endocrine system
endocrine system diseases
Chemistry
Cell growth
Caspase 3
Cell cycle
medicine.disease
female genital diseases and pregnancy complications
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Oncology
Apoptosis
Cell culture
030220 oncology & carcinogenesis
medicine
Cancer research
Pharmacology (medical)
Ovarian cancer
Protein kinase B
PI3K/AKT/mTOR pathway
Subjects
Details
- ISSN :
- 11786930
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- OncoTargets and Therapy
- Accession number :
- edsair.doi...........10697db674690114fe6cdea726db78fd