ArticlePloS one2020
Silencing miR-202-3p increases MMP-1 and promotes a brain invasive phenotype in metastatic breast cancer cells.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
- SPANXB1 drives brain metastasis in breast cancer via MMP1 regulation: potential therapeutic insights with metformin.Cell death discovery · 2025Article
- Network Pharmacology Approaches Used to Identify Therapeutic Molecules for Chronic Venous Disease Based on Potential miRNA Biomarkers.Journal of xenobiotics · 2024Article
- MiRNAs as new potential biomarkers and therapeutic targets in brain metastasis.Non-coding RNA research · 2024Review
- Protecting the Brain: Novel Strategies for Preventing Breast Cancer Brain Metastases through Selective Estrogen Receptor β Agonists and In Vitro Blood-Brain Barrier Models.International journal of molecular sciences · 2024Article
- Crosstalk between breast cancer-derived microRNAs and brain microenvironmental cells in breast cancer brain metastasis.Frontiers in oncology · 2024Review
- New insights of miRNA molecular mechanisms in breast cancer brain metastasis and therapeutic targets.Non-coding RNA research · 2023Article
- Exosomes Interactions with the Blood-Brain Barrier: Implications for Cerebral Disorders and Therapeutics.International journal of molecular sciences · 2023Review
- Upregulation of Matrix Metalloproteinases in the Metastatic Cascade of Breast Cancer to the Brain.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Causal relationships between serum matrix metalloproteinases and estrogen receptor-negative breast cancer: a bidirectional mendelian randomization study.Scientific reports · 2023Article
- Extracellular Vesicle-Packaged miR-195-5p Sensitizes Melanoma to Targeted Therapy with Kinase Inhibitors.Cells · 2023Article
- Molecular Heterogeneity of the Brain Endothelium.Current issues in molecular biology · 2023Article
- Review
- Insights into Exosome Transport through the Blood-Brain Barrier and the Potential Therapeutical Applications in Brain Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Review
- Molecular landscape and emerging therapeutic strategies in breast cancer brain metastasis.Therapeutic advances in medical oncology · 2023Review
- MiR-202-3p inhibits the proliferation and metastasis of lung adenocarcinoma cells by targeting RRM2.Annals of translational medicine · 2022Article
- The microRNA-202 as a Diagnostic Biomarker and a Potential Tumor Suppressor.International journal of molecular sciences · 2022Review
- Exosomal MMP-1 transfers metastasis potential in triple-negative breast cancer through PAR1-mediated EMT.Breast cancer research and treatment · 2022Article
- MicroRNAs as therapeutic targets in breast cancer metastasis.Drug delivery and translational research · 2022Review
- HPRT1 Promotes Chemoresistance in Oral Squamous Cell Carcinoma via Activating MMP1/PI3K/Akt Signaling Pathway.Cancers · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBrain metastasis (BM) is a major cause of morbidity and mortality in breast cancer (BC) and its molecular mechanism remains poorly understood. Transmigration of metastatic cells through the brain endothelium is an essential step in BM. Metalloproteinase-1 (MMP-1) overexpression plays a key role in promoting trans-endothelial migration by degrading the inter-endothelial junctions and disrupting the endothelial integrity. However, little is known about the molecular mechanisms that induce MMP-1 in metastatic cells granting them a brain invasive phenotype. MiR-202-3p is downregulated in brain metastases compared to primary breast tumors and directly targets MMP-1. Here, we unraveled a critical role of miR-202-3p loss in MMP-1 upregulation promoting transmigration of metastatic cells through the brain endothelium.
methodsA variant of the MDA-MB-231 human BC cell line (MDA-MB-231-BrM2) selected for its propensity to form brain metastases was found to express high levels of MMP-1 and low levels of miR-202-3p compared to the parental cells. Using a gain-and-loss of function approach, we modulated levels of miR-202-3p and examined the resultant effect on MMP-1 expression. Effect of miR-202-3p modulation on integrity of the brain endothelium and the transmigrative ability of BC cells were also examined.
resultsLoss of miR-202-3p in breast cancer cells enhanced their transmigration through the brain endothelium by upregulating MMP-1 and disrupting the inter-endothelial junctions (claudin-5, ZO-1 and ß-catenin). Restoring miR-202-3p exerted a metastasis-suppressive effect and preserved the endothelial barrier integrity.
conclusionsOur study identified a critical regulatory role of miR-202-3p in brain metastasis and shed light on miR-202-3p/MMP-1 axis as a novel prognostic and therapeutic target that can be exploited to predict and prevent brain metastasis in breast cancer patients.
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