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

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.

BCAP29/31 as a Poor Prognostic Biomarker for Head and Neck Squamous Carcinoma: Impacting the TGFβ1/Smad- EMT Pathway

“…The functions of the genes that appear to be common in the BCAP29/31 reciprocal network have also been explored to some extent. Among them, STT3A and STT3B may induce endoplasmic reticulum stress-dependent apoptosis in breast cancer [51], and TMED10 has been shown to act as a biomarker of poor prognosis in HNSC [52], these results suggest that in HNSC, BCAP29/31 may still play a synergistic role at the level of endoplasmic reticulum output and quality control, and have a prognostic situation.…”

Terminal Unfolded Protein Responses-related genes predict prognosis and associate with proliferation and apoptosis in clear cell renal cell carcinoma

“…46 Current studies have shown that the OST complex is involved in the maintenance of the ER homeostasis, and the loss or abnormal function of its composition affects the ER stress state in cells. 15 Wen et al 47 found that the lack of STT3A in human embryonic kidney cells HEK293 caused ER stress and activated the UPR pathway, and Ding et al 48 found that the loss of RPN1, a non-catalytic subunit of the OST complex, caused ER stress-mediated apoptosis in breast cancer cells.…”

Disulfidptosis-related lncRNAs predict prognosis and immune response of Liver hepatocellular carcinoma

“…N-linked glycosylation is an important protein modi cation in eukaryotic cells, and Nglycosylation is carried out in the lumen of the endoplasmic reticulum through the oligosaccharyltransferase (OST) complex. Since RPN1 is only present in the rough endoplasmic reticulum and promotes N-glycosylation by selecting speci c substrates, there are fewer research results in cancer-related studies [25] .In the SLC family human genome,SLC3A2 is the second largest membrane protein family.SLC3A2 functions by forming a heterodimeric complex with the light subunits LAT1 and LAT2, which primarily have encoded CD98hc, forming an amino acid transport protein [26] .SLC3A2 regulates the mTORC1 pathway and cellular metabolism by regulating LAT1/LAT2 stability and plasma membrane localization, leading to glutamine and leucine uptake [27] .SLC7A11 is a key component of the cystine/glutamate reverse transport system xc-and is essential for cystine uptake, glutathione (GSH) synthesis [28] .…”