ArticleInternational journal of molecular sciences2024
Extracellular Vesicles from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients Deliver MiR-21 and Induce Methotrexate Resistance in Lung Cancer Cells.
Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- Systematic review of extracellular vesicle-based liquid biopsy for leptomeningeal metastasis: current evidence and future directions.Clinical & experimental metastasis · 2026Pooled it
- Protease inhibition: breaking the barriers of chemoresistance in cancer.Molecular biology reports · 2026Review
- Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review).Oncology letters · 2026Review
- Engineered MSC-Exosomes Delivering miRNAs for Respiratory Disease Diagnostics and Therapy: Opportunities and Challenges.International journal of nanomedicine · 2026Review
- Toxicological Effects of Titanium Dioxide Nanoparticles on Human Menstrual Blood Mesenchymal Stem Cells.International journal of molecular sciences · 2025Article
- Profiling extracellular vesicles from cerebrospinal fluid for classification of intradural spinal tumors.Scientific reports · 2025Article
- MicroRNA‑21: A potential therapeutic target in lung cancer (Review).International journal of oncology · 2025Review
- Role of M2 macrophage-derived exosomes in cancer drug resistance via noncoding RNAs.Discover oncology · 2025Review
- [Brain and Meningeal Metastases of Lung Cancer Manifested as Brain Calcifications: A Case Report and Literature Review].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- RNA-binding proteins and exoribonucleases modulating miRNA in cancer: the enemy within.Experimental & molecular medicine · 2024Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Leptomeningeal metastasis (LM) is a common and fatal complication of advanced non-small cell lung cancer (NSCLC) caused by the spread of malignant cells to the leptomeninges and cerebrospinal fluid (CSF). While intra-CSF methotrexate (MTX) chemotherapy can improve prognosis, eventual MTX resistance deters continued chemotherapy. Recent studies have shown that increased miRNA-21 (miR-21) expression in the CSF of patients with LM after intraventricular MTX-chemotherapy is associated with poor overall survival; however, the molecular mechanisms underlying this resistance are poorly understood. Here, we confirm, in 36 patients with NSCLC-LM, that elevated miR-21 expression prior to treatment correlates with poor prognosis. MiR-21 overexpression or sponging results in a corresponding increase or decrease in MTX resistance, demonstrating that cellular miR-21 expression correlates with drug resistance. MiR-21-monitoring sensor and fluorescent extracellular vesicle (EV) staining revealed that EV-mediated delivery of miR-21 could modulate MTX resistance. Moreover, EVs isolated from the CSF of LM patients containing miR-21 could enhance the cell proliferation and MTX resistance of recipient cells. These results indicate that miR-21 can be transferred from cell-to-cell via EVs and potentially modulate MTX sensitivity, suggesting that miR-21 in CSF EVs may be a prognostic and therapeutic target for overcoming MTX resistance in patients with NSCLC-LM.
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Registered trials
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