PSMC2/CCND1 axis promotes development of ovarian cancer through regulating cell growth, apoptosis and migration

Dawei Zhu,Jie Huang,Wei Li,Ning Liu,Limei Yan

doi:10.1038/s41419-021-03981-5

Abstract

Ovarian cancer is known as one of the most common malignancies of the gynecological system, whose treatment is still not satisfactory because of the unclear understanding of molecular mechanism. PSMC2 is an essential component of 19 S regulatory granules in 26 S proteasome and its relationship with ovarian cancer is still not clear. In this study, we found that PSMC2 was upregulated in ovarian cancer tissues, associated with tumor grade and could probably predict poor prognosis. Knocking down the endogenous PSMC2 expression in ovarian cancer cells could decrease colony formation ability, cell motility and cell proliferation rate, along with increasing cell apoptosis rate. Cells models or xenografts formed by cells with relatively lower expression of PSMC2 exhibited weaker oncogenicity and slower growth rate in vivo. Moreover, gene microarray was used to analyze the alteration of gene expression profiling of ovarian cancer induced by PSMC2 knockdown and identify CCND1 as a potential downstream of PSMC2. Further study revealed the mutual regulation between PSMC2 and CCND1, and demonstrated that knockdown of CCND1 could enhance the regulatory effects induced by PSMC2 knockdown and overexpression of CCND1 reverses it. In summary, PSMC2 may promote the development of ovarian cancer through CCND1, which may predict poor prognosis of ovarian cancer patients.

Highlights

Ovarian cancer is the gynecological malignant tumor with high mortality rates, of which epithelial ovarian cancer is the most important pathological types [1]
Data collected from TCGA database potentiate the relationship between PSMC2 level and poor prognosis of patients with ovarian cancer
Loss-offunction assays performed on ovarian cancer cells with or without PSMC2 knockdown illustrated that PSMC2 may promote the progress of ovarian cancer by means of promoting cell proliferation, colony formation, cell migration and alleviating cell apoptosis

Summary

INTRODUCTION

Ovarian cancer is the gynecological malignant tumor with high mortality rates, of which epithelial ovarian cancer is the most important pathological types [1]. Ovarian cancer is one of the three considerable malignancies of the female reproductive system It is characterized by complex histopathology, high degree of malignancy and poor survival prognosis. Proteasome 26 S subunit ATPase 2 (PSMC2) is one of the essential components of 19 S subunit It has the functions of ATP binding, nucleotide binding, nucleoside triphosphatase and hydrolase. 1234567890();,: This study was accomplished for the purpose of getting insight RT-qPCR into the role and mechanism of PSMC2 in ovarian cancer development. Survival analysis based on data collected from TCGA indicated the potential linkage between PSMC2 high expression and poor prognosis of patients with ovarian cancer. In vitro and in vivo assays elucidated that silencing PSMC2 could significantly inhibit ovarian cancer development through regulating cell growth, apoptosis and migration. ECL plusTM Western blotting system kit from Amersham was used for color developing and target proteins detecting and bands were analyzed with ImageJ software

MATERIALS AND METHODS

Zhu et al 3

Findings

DISCUSSION