Knockdown of Oligosaccharyltransferase Subunit Ribophorin 1 Induces Endoplasmic-Reticulum-Stress-Dependent Cell Apoptosis in Breast Cancer.

Jiajun Ding,Jiahui Xu,Rui Zhang,Xueyan He,Lixing Zhang,Qiaodan Deng,Suling Liu,Wei Ma

doi:10.3389/fonc.2021.722624

Abstract

Ribophorin 1 (RPN1) is a major part of Oligosaccharyltransferase (OST) complex, which is vital for the N-linked glycosylation. Though it has been verified that the abnormal glycosylation is closely related to the development of breast cancer, the detail role of RPN1 in breast cancer remains unknown. In this study, we explored the public databases to investigate the relationship between the expression levels of OST subunits and the prognosis of breast cancer. Then, we focused on the function of RPN1 in breast cancer and its potential mechanisms. Our study showed that the expression of several OST subunits including RPN1, RPN2, STT3A STT3B, and DDOST were upregulated in breast cancer samples. The protein expression level of RPN1 was also upregulated in breast cancer. Higher expression of RPN1 was correlated with worse clinical features and poorer prognosis. Furthermore, knockdown of RPN1 suppressed the proliferation and invasion of breast cancer cells in vitro and induced cell apoptosis triggered by endoplasmic reticulum stress. Our results identified the oncogenic function of RPN1 in breast cancer, implying that RPN1 might be a potential biomarker and therapeutic target for breast cancer.

Highlights

Breast cancer (BC) is one of the leading causes for the mortality of women all over the world
Further functional analysis showed that the 12 central genes we focused on were as expected greatest related to the OST complex and the function of glycosylation
Higher mRNA expression levels of Ribophorin 2 (RPN2), defender against cell death 1 (DAD1), oligosaccharyltransferase complex (OSTC), keratinocyte associated protein 2 (KRTCAP2) and lower expression levels of tumor suppressor candidate 3 (TUSC3), magnesium transporter 1 (MAGT1) could be found in different types of BC compared to the normal breast tissues in Curtis’s dataset [22], Zhao’s dataset [24], Ma’s dataset [25], Finak’s dataset [26], Karnoub’s dataset [27], and TCGA dataset

Summary

Introduction

Breast cancer (BC) is one of the leading causes for the mortality of women all over the world. It accounted for 24.2% of the 8.6 million new cases of female cancer and 15.0% of 4.2 million cancerrelated deaths in women worldwide in 2018 [1]. Large accessible databases like Oncomine have become efficient and economic tools for identifying targets for BC [3, 4]. They may play an important role in identifying novel genes associated with BC

Methods

Results

Conclusion