Loss of RPN1 Promotes Antitumor Immunity via PD-L1 Checkpoint Blockade in Triple-negative Breast Cancer--Experimental Studies.

IF 12.5 2区 医学 Q1 SURGERY
Mengxue Wang, Xunjia Li, Yushen Wu, Long Wang, Xue Zhang, Meng Dai, Yang Long, Deyu Zuo, Shengwei Li, Xuedong Yin
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引用次数: 0

Abstract

Background: RPN1, also known as ribophorin I (RPN1), is a type I transmembrane protein that plays an important role in glycosylation. However, the effects of RPN1 on cancer progression and immune evasion in breast cancer (BC) have not been identified.

Materials and methods: The expression of RPN1 was evaluated using RT-qPCR and immunohistochemistry (IHC). The effects of RPN1 on tumor cells were assessed using RT-qPCR, western blotting, flow cytometry, Cell Counting Kit 8 (CCK-8), colony formation assays, and in vivo experiments. The mechanism by which RPN1 modifies programmed death ligand-1 (PD-L1) and the tumor microenvironment was examined by RT-qPCR, western blotting, co-immunoprecipitation (Co-IP), and flow cytometry. The influence of the transcription factor YY1 on RPN1 expression was revealed using bioinformatics analysis, RT-qPCR, and dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays.

Results: RPN1 is aberrantly expressed in triple-negative breast cancer (TNBC) cells, correlating with increased proliferation and poor prognosis. RPN1 mediates the post-translational modification of PD-L1, enhancing its glycosylation and stability, thus facilitating PD-L1-mediated immune escape and tumor growth. The deletion of RPN1 improves the TNBC microenvironment and enhances the efficacy of anti-PD-1 therapy. Additionally, we uncovered a novel regulatory axis involving YY1/RPN1/YBX1 in PD-L1 regulation, affecting TNBC growth and metastasis.

Conclusions: Our preliminary study reveals that targeting RPN1 promotes immune suppression, providing a new potential immunotherapy strategy for TNBC. However, further research is necessary to fully elucidate and understand the specific mechanisms of RPN1 in TNBC and its potential for clinical application .

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来源期刊
CiteScore
17.70
自引率
3.30%
发文量
0
审稿时长
6-12 weeks
期刊介绍: The International Journal of Surgery (IJS) has a broad scope, encompassing all surgical specialties. Its primary objective is to facilitate the exchange of crucial ideas and lines of thought between and across these specialties.By doing so, the journal aims to counter the growing trend of increasing sub-specialization, which can result in "tunnel-vision" and the isolation of significant surgical advancements within specific specialties.
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