Oncogenic Role of NUPR1 in Ovarian Cancer

Jiangtao Yu; Haiyan Zhu; Rui Li; Qi Jiang; Wenqing Luan; Juanjuan Shi; Peishu Liu

doi:10.2147/OTT.S262224

Oncogenic Role of NUPR1 in Ovarian Cancer

Onco Targets Ther. 2020 Nov 30:13:12289-12300. doi: 10.2147/OTT.S262224. eCollection 2020.

Authors

Jiangtao Yu^#^{1

2}, Haiyan Zhu^#^{2

3}, Rui Li¹, Qi Jiang^{2

4}, Wenqing Luan¹, Juanjuan Shi¹, Peishu Liu¹

Affiliations

¹ Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People's Republic of China.
² Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, People's Republic of China.
³ Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200126, People's Republic of China.
⁴ Department of Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People's Republic of China.

^# Contributed equally.

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.

Keywords: AKT; NUPR1; invasion; migration; ovarian cancer; proliferation.