Journal
FRONTIERS IN NEUROSCIENCE
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2018.00602
Keywords
microRNA-298; P-glycoprotein; antiepileptic drugs; multidrug resistance; refractory epilepsy
Categories
Funding
- National Natural Science Foundation of China [81571261]
- Shanghai Municipal Commission of Health and Family Planning [20164Y0030]
- Shanghai Committee of Science and Technology [14411972500]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available