ArticleJournal of experimental & clinical cancer research : CR2025
MRPL21-PARP1 axis promotes cisplatin resistance in head and neck squamous cell carcinoma by inhibiting autophagy through the PI3K/AKT/mTOR signaling pathway.
Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- LEF1/NFE2L3/TACC1 axis activates the AKT-mTOR pathway to promote the progression of esophageal squamous cell carcinoma.Journal of thoracic disease · 2026Article
- Dynamic collaboration between mitochondria and organelles: mechanisms, functions, and disease implications.Apoptosis : an international journal on programmed cell death · 2026Review
- CC223 enhances cisplatin sensitivity of platinum-resistant ovarian cancer by inducing cell cycle arrest.Journal of ovarian research · 2026Article
- CAV2 Modulates Cetuximab Sensitivity in HNSCC via Ubiquitin-Mediated Disruption of the PACT-PKR Axis.Cancers · 2026Article
- Hydroxysafflor yellow a attenuates oxygen-glucose deprivation/ reoxygenation induced endothelial pyroptosis via PARP-1/NLRP3 pathway.Frontiers in pharmacology · 2026Article
- Characterization of ANXA1 in chemotherapy resistance of head and neck squamous cell carcinoma: insights from artificial intelligence and integrative bioinformatics analysis.Frontiers in cell and developmental biology · 2026Article
- Integrating CT radiomics and transcriptomics: a biologically-informed machine learning model for predicting chemotherapy response in advanced laryngeal cancer.Frontiers in oncology · 2026Article
- CDCSI: a machine learning-based interpretable cell death and cellular senescence index for prognosis improvement, immune landscape characterization, and therapeutic response prediction in head and neck squamous cell carcinoma.Frontiers in immunology · 2026Article
- PARPs and PARP inhibitors: molecular mechanisms and clinical applications.Molecular biomedicine · 2025Review
- Mitochondrial dynamics in cisplatin resistance: molecular mechanisms and therapeutic targeting.Frontiers in oncology · 2025Review
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Authors and funding
13 authors.
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Abstract
backgroundHead and neck squamous cell carcinoma (HNSCC) constitutes a major clinical challenge that severely affects patient survival. Mitochondrial ribosomal protein (MRP) family plays an important role in energy metabolism by participating in mitochondrial oxidative phosphorylation. However, their roles in HNSCC and the underlying mechanisms are still unclear.
methodsSingle-cell analysis highlighted MRPL21 as a notable biomarker of HNSCC. Human HNSCC tissues, cell lines, and xenograft models in nude mice were used to explore the expression and function of MRPL21. The mass spectrometry was performed to analyze the potential binding targets of MRPL21. In vitro and in vivo experiments were performed to evaluate the effect of MRPL21 on autophagy and cisplatin resistance. The inhibitory actions of siMRPL21 nanodelivery systems on HNSCC progression were also evaluated in vivo.
resultsClinically, relatively high expression level of MRPL21 was associated with poor prognosis in HNSCC patients, and overexpression of MRPL21 significantly promoted HNSCC tumorigenesis, metastasis, and cisplatin resistance. Mechanistically, MRPL21 upregulated mitochondrial oxidative phosphorylation (OXPHOS) and increased PARylation level, inhibited autophagy through activating the downstream PI3K/AKT/mTOR signaling pathway, and ultimately led to tumor progression and cisplatin resistance in HNSCC.
conclusionWe conclude that MRPL21 is a novel biomarker and therapeutic target of HNSCC progression and cisplatin resistant, which may provide a new approach for overcoming cisplatin resistance in HNSCC patients.
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