miR-23a-3p is involved in drug resistance by directly targeting the influx drug transporter organic anion-transporting polypeptide 2
Abstract
Objective Drug transporters are involved in the drug resistance of individuals with drug-resistant epilepsy by influencing the intracerebral transport of antiepileptic drugs (AEDs). The expression of drug transporters is associated with microRNAs. We previously revealed that miR-23a-3p levels were elevated in the blood of patients with intractable epilepsy. Additionally, the influx drug transporter organic anion-transporting polypeptide 2 (Oatp2) is involved in the intracerebral transport of valproic acid (VPA), the most commonly used AED; repeated seizures lead to decreased expression of Oatp2. However, the role of miR-23a-3p in the expression of Oatp2 and in the development of drug resistance has not been established. Herein, we aimed to determine the potential role of miR-23a-3p in VPA-resistant epilepsy through in vivo and in vitro experiments. Methods Epilepsy was elicited after status epilepticus (SE) was induced by lithium-pilocarpine in adult Sprague-Dawley rats, followed by VPA treatment to select rats with VPA resistance. The expression of miR-23a-3p was detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). A miR-23a-3p inhibitor was intracerebrally injected into VPA-resistant rats, and histological staining and Morris water maze tests were performed to evaluate brain damage and learning/memory functions in these rats. Subsequently, a dual-luciferase reporter assay and a VPA uptake assay were performed in brain microvascular…
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Intracerebral injection of miR-23a-3p inhibitors can reduce brain damage and the related learning and memory deficits in valproic acid (VPA) resistance rat models.
“Intracerebral injection of miR-23a-3p inhibitors can reduce brain damage and the related learning and memory deficits in valproic acid (VPA) resistance rat models.”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [137]
Oatp2 is a direct target of miR-23a-3p.
“The influx drug transporter organic anion-transporting polypeptide 2 (Oatp2), is a direct target of miR-23a-3p.”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [137]
miR-23a-3p negatively regulates Oatp2 in brain microvascular endothelial cells (BMECs), leading to reduced VPA uptake in intractable epilepsy.
“The miR-23a-3p negatively regulates Oatp2 in the brain microvascular endothelial cells (BMECs), leading to reduced VPA uptake in intractable epilepsy [136,137].”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [137]
Cites
Sui, D.-M., Xie, Q., Yi, W.-J., Gupta, S., Yu, X.-Y., Li, J.-B., Wang, J., Wang, J.-F., & Deng, X.-M. (2016) · Mediators of Inflammation · doi:10.1155/2016/1045657 · Cited by 124 · see citing works
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Recent advances of miR-23 in human diseases and growth development
Qian, X., Jiang, Y., Yang, Y., Zhang, Y., Xu, N., Xu, B., Pei, K., Yu, Z., & Wu, W. (2025) · Non-coding RNA Research · doi:10.1016/j.ncrna.2024.12.010 · Cited by 5 · see citing works
- Authors
- Guo, Y., Li, J., Kang, Y., & Jiang, L.
- Affiliations
- Children's Hospital of Chongqing Medical University (CN)
- Chongqing Medical University (CN)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Guo, Yi
- Venue
- Child's Nervous System
- Published
- 2021-03-29
- Volume
- 37
- Issue
- 8
- Pages
- 2545-2555
- ISSN
- 0256-7040 (ISSN-L)
- 1433-0350
- OpenAlex
- W3151771776
- Cited by
- 9
- References
- 1
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Child s Nervous System (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Young Scientists Fund (81701277)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- OATP2, drug resistance, drug-resistant epilepsy, valproic acid, antiepileptic drugs, drug transporters, microRNA, brain microvascular endothelial cells, status epilepticus, learning and memory impairment, brain damage
- MeSH terms
- Animals, Anions, Drug Resistance, Humans, Peptides, Rats, Sprague-Dawley, Organic Anion Transporters, MicroRNAs, Endothelial Cells, Rats
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