Overexpression of PSMC2 promotes the tumorigenesis and development of human breast cancer via regulating plasminogen activator urokinase (PLAU)

Yanyan Wang,Haihong Jing,Jingruo Li,Yuanting Gu,Jing Wang,Mingzhi Zhu,Youyi Xiong

doi:10.1038/s41419-021-03960-w

Abstract

Emerging evidence has declared that Proteasome 26S subunit ATPase 2 (PSMC2) is involved in tumor progression. However, its role in breast cancer has not been investigated. Therefore, we sought to establish a correlation between breast cancer and PSMC2. PSMC2 expression in tissues was detected by immunohistochemistry. Loss-of-function study was used to evaluate the effects of PSMC2 knockdown in cell proliferation, apoptosis and migration. A gene microarray was performed to explore the potential downstream of PSMC2 with the help of Ingenuity Pathway Analysis (IPA). The effects of the PSMC2/PLAU axis on breast cancer were examined in vitro. Compared to para-cancer tissues, PSMC2 level was considerably elevated in breast cancer, which was significantly correlated with tumor grade. Knockdown of PSMC2 suppressed breast cancer progression in vitro and in vivo. The mechanistic research revealed that PSMC2 promotes the development and progression of human breast cancer through interacting with PLAU. Outcomes of our study showed that overexpression of PSMC2 provide tumorigenic and metastatic advantages in breast cancer, which may involve the regulation of PLAU. This study not only reveals a critical mechanism of breast cancer development, but also provides a promising therapeutic target for breast cancer treatment.

Highlights

Breast cancer (BC) is the most common cancer in women throughout the world and the second leading cause of cancerrelated deaths after lung cancer [1, 2]
Diseases and functions, molecular and cellular processes that are significantly associated with differentially expressed genes (DEGs) in the data sets were determined using Ingenuity Pathway Analysis (IPA) software. |Z score | > 2 is significant
Tumor size ≤3 cm >3 cm RESULT High expression of PSMC2 is associated with aggressive phenotypes in human breast cancer In order to investigate the PSMC2 expression level in breast cancer specimens, a breast cancer tissue microarray consisting of 173 breast cancer samples and 35 para-carcinoma samples was used for IHC staining

Summary

INTRODUCTION

Breast cancer (BC) is the most common cancer in women throughout the world and the second leading cause of cancerrelated deaths after lung cancer [1, 2]. PLAU, encoding urokinase-type plasminogen activator (uPA), does not have kinase activity, but functions as a protease, and belongs to the PA family serine protease. It is mainly responsible for the transformation of plasminogen to plasmin, the hydrolysis of extracellular matrix remodeling related proteins and the activation of growth factors. 1234567890();,: complementary molecular approaches in multiple cellular models Technology Co., Ltd) or PLAU overexpression construct

MATERIALS AND METHODS

RESULT

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ETHICS STATEMENT