ArticleFrontiers in neuroscience2018
MicroRNA-298 Reverses Multidrug Resistance to Antiepileptic Drugs by Suppressing MDR1/P-gp Expression
Article in Frontiers in neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- MiR-298 suppresses astrocytic NF-κB activity and neuroinflammationThe Korean journal of pain · 2025Article
- Progress in Epigenetic Modification Regulating Drug Transporters in the Hypoxic Environment.Current drug delivery · 2025Review
- Tumor-derived exosome PPP3CB induce gemcitabine resistance by regulating miR-298/STAT3 in pancreatic cancer.Heliyon · 2024Article
- Efflux ABC transporters in drug disposition and their posttranscriptional gene regulation by microRNAs.Frontiers in pharmacology · 2024Review
- Evaluation of P-glycoprotein-targeting circulating microRNAs as peripheral biomarkers for medically intractable epilepsy.Acta epileptologica · 2023Article
- Regulation of P-Glycoprotein in the Brain.International journal of molecular sciences · 2022Review
- A Novel Drug Modulator Diarylheptanoid (International journal of molecular sciences · 2022Article
- Transporter Regulation in Critical Protective Barriers: Focus on Brain and Placenta.Pharmaceutics · 2022Review
- Aberrant expression of miRNAs in epilepsy.Molecular biology reports · 2022Review
- P-glycoprotein: new insights into structure, physiological function, regulation and alterations in disease.Heliyon · 2022Review
- LncRNA Neat1/miR-298-5p/Srpk1 Contributes to Sevoflurane-Induced Neurotoxicity.Neurochemical research · 2021Article
- miR-485's anti-drug resistant epilepsy effects by regulating SV2A/PSD-95 and targeting ABCC1 and neuronal signaling-transduction proteins in hippocampus of rats.Brain and behavior · 2021Article
- Review
- MicroRNA-Based Therapeutics for Drug-Resistant Colorectal Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- MicroRNA-1246 by Targeting AXIN2 and GSK-3β Overcomes Drug Resistance and Induces Apoptosis in Chemo-resistant Leukemia Cells.Journal of Cancer · 2021Article
- The roles of the human ATP-binding cassette transporters P-glycoprotein and ABCG2 in multidrug resistance in cancer and at endogenous sites: future opportunities for structure-based drug design of inhibitors.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Novel Intrinsic Mechanisms of Active Drug Extrusion at the Blood-Brain Barrier: Potential Targets for Enhancing Drug Delivery to the Brain?Pharmaceutics · 2020Review
- Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and Astrocytes Under Hypoxic Conditions.Frontiers in behavioral neuroscience · 2020Article
- The year in review: progress in brain barriers and brain fluid research in 2018.Fluids and barriers of the CNS · 2019Article
- The Potential for microRNA Therapeutics and Clinical Research.Frontiers in genetics · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P-glycoprotein (P-gp), a critical multidrug transporter, recognizes and transports various antiepileptic drugs (AEDs) through the blood-brain barrier (BBB). This may decrease the concentrations of AEDs in brain tissues and cause multidrug resistance (MDR) in patients with refractory epilepsy. Compelling evidence indicates that microRNAs (miRNAs) modulate MDR in various cancers by regulating P-gp expression. Furthermore, a previous study showed that miR-298 mediates MDR in breast cancer cells by downregulating P-gp expression. Based on the therapeutic results obtained from tumor cells, we aimed to determine whether miR-298 reverses MDR to AEDs by regulating P-gp expression in the BBB. We first established different drug-resistant cell lines, including PHT-resistant HBMECs (human brain microvascular endothelial cells) and doxorubicin (DOX)-resistant U87-MG (human malignant glioma) cells, by inducing P-gp overexpression. Quantitative real-time PCR (qRT-PCR) analysis revealed reduced expression of miR-298 in both HBMEC/PHT and U87-MG/DOX cells, and the luciferase reporter assay identified the direct binding of miR-298 to the 3'-untranslated region (3'-UTR) of P-gp. Moreover, ectopic expression of miR-298 downregulated P-gp expression at the mRNA and protein levels, thereby increasing the intracellular accumulation of AEDs in drug-resistant HBMEC/PHT and U87-MG/DOX cells. Thus, our findings suggest that miR-298 reverses MDR to AEDs by inhibiting P-gp expression, suggesting a potential target for overcoming MDR in refractory epilepsy.
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