Co-targeting MRPS7-23 synergistically enhances cisplatin efficacy to suppress nasopharyngeal carcinoma growth and metastasis

Sep 23, 2026

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Cisplatin-based chemoradiotherapy regimens for advanced nasopharyngeal carcinoma remain standard, yet 30–40% of patients develop intrinsic chemoresistance, whose molecular basis is unclear. Integrative multi-omics profiling identified MRPS7 and MRPS23 as novel drivers of cisplatin resistance. Mechanistically, multi-level evidence shows MRPS7/23 inhibit β-catenin ubiquitination, sustaining β-catenin-mediated cancer stemness and EMT. USP10 protects MRPS7/23 from proteasomal degradation, while Spautin-1 synergizes with cisplatin to reduce tumor growth and metastasis in mice, supporting the USP10-MRPS7/23-β-catenin axis for precision therapy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages25

Reading Time1 h 3 min

AccessFree to download

Abstract

Keywords

Introduction

Cisplatin resistance and EMT/cancer stemness

MRPS proteins and their role in NPC

Ivyspring International Publisher InternationalJournal of Biological Sciences 2026; 22(2): 970-994. doi: 10.7150/ijbs.115523 Research Paper Co-targeting MRPS7-23 synergistically enhancescisplatin efficacy to suppress nasopharyngeal carcinoma growth and metastasis Zhangqi Cao1,2,3†, Can Pan2†, Zeyu Liu1,2,3†, Qi Quan1,2,3, Mengping Li1,2,3, Yu Huang2,4, Chuwen Liang1,2,3, Yuwen Chen1,2,3, Teng Fan1,2,3, Ping Chen1,2,3, Fu Kai 2, Shuangli Zhu2, Sijia Li2, Xin Su1,2,3, Fang Wang2, Liwu Fu2􀀍, Bei Zhang1,2,3􀀍 1. TCM&VIP Department, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. 2. State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. 3. Integrated Traditional Chinese and Western Medicine Research Center, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. 4. Department of Pharmacy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. †These authors contributed equally to this work. 􀀍 Corresponding author: Prof. Liwu Fu, [fulw@mail.sysu.edu.cn](fulw@mail.sysu.edu.cn); Prof. Bei Zhang, [zhangbei@sysucc.org.cn](zhangbei@sysucc.org.cn). © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions. Received: 2025.04.10; Accepted: 2025.11.25; Published: 2026.01.01 Abstract While cisplatin-based chemoradiotherapy regimens (gemcitabine-cisplatin [GP] and docetaxel-cisplatin-5-fluorouracil [TPF]) remain standard treatments for advanced nasopharyngeal carcinoma (NPC), 30-40% of patients exhibit intrinsic chemoresistance, resulting in therapeutic failure. The molecular underpinnings ofthis resistance are poorly characterized. Through integrative multi-omics profiling, we identified Mitochondrial Ribosomal Protein S7 (MRPS7) and Mitochondrial Ribosomal Protein S23 (MRPS23) as novel drivers of cisplatin resistance in NPC. Mechanistically, integrated single-cell RNA-seq (scRNA-seq) analysis, mass spectrometry, and functional studies revealed that MRPS7 and MRPS23 stabilized β-catenin by inhibiting its ubiquitination, thereby promoting β-catenin-mediated cancer stemness and epithelial-mesenchymal transition (EMT) to establish cisplatin resistance in NPC. Additionally, we identified Ubiquitin Specific Peptidase 10 (USP10) as a critical upstream regulator that protects MRPS7/23 from proteasomal degradation and sustaining their oncogenic activity. Notably, Spautin-1, a potent USP10 inhibitor, demonstrates synergistic therapeutic activity with cisplatin in diminished tumor growth and metastasis in NPC mice. This research established the USP10-MRPS7/MRPS23-β-catenin axis as a promising precision medicine strategy to combat metastatic dissemination and reverse cisplatin chemoresistance in advanced NPC, which offers a promising opportunity to develop cisplatin sensitizers for the clinical translation of NPC therapies. Keywords: MRPS7, MRPS23, nasopharyngeal carcinoma, cisplatin resistance, metastasis Introduction NPC is a unique form of head and necksquamous cell carcinoma (HNSC), characterized by high malignancy and close link to Epstein-Barr virus (EBV) infection. Its incidence is particularly high in Southeast Asia, creating a critical demand for the discovery of new prognostic biomarkers and treatment approaches to enhance patient outcomes[1-3] . The multicenter phase III randomized controlled trial evaluating induction chemotherapy strategies in locoregionally advanced NPC revealed that the GP regimen significantly outperformed the conventional TPF combination in terms of OS, potentiall

FAQs

What problem does the study address in nasopharyngeal carcinoma?

The study addresses intrinsic cisplatin resistance in advanced nasopharyngeal carcinoma, which leads to therapeutic failure and poor outcomes.

Which genes are identified as drivers of cisplatin resistance?

Integrative multi-omics profiling identifies MRPS7 and MRPS23 as novel drivers of cisplatin resistance in nasopharyngeal carcinoma.

How do MRPS7 and MRPS23 influence cisplatin response mechanistically?

MRPS7/23 stabilize β-catenin by inhibiting its ubiquitination, promoting β-catenin-mediated cancer stemness and EMT, which together establish cisplatin resistance.

Sep 23, 2026

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