Neuroprotective Effects of lncRNA EPB41L4A-AS1 Against Ischemic Stroke Injury Through Regulating Microglial State Transition and Ferroptosis via miR-214-3p/GPX4 Axis.

Authors

Ying Guo, Jinyuan Yi, Haitao Fang, Yu Zhang, Haixiao Zhang

Published in

Neurochemical research. Volume 51. Issue 4. Jul 10, 2026. Epub Jul 10, 2026.

Abstract

Long non-coding RNAs (lncRNAs) regulate microRNAs and their target genes to control key pathological processes after acute ischemic stroke (AIS). To investigate lncRNA EPB41L4A-AS1's role in microglial function via miR-214-3p/GPX4, and its clinical relevance as a prognostic indicator in AIS. EPB41L4A-AS1 levels were measured by RT-qPCR in 120 AIS patients and OGD/R-treated BV2 microglia. ELISA and western blot were employed to assess microglial state transition and ferroptosis in OGD/R-injured BV2 cells. A combination of RIP, RNA pull-down, and luciferase reporter assays were employed to validate the miRNA and gene targets regulated by EPB41L4A-AS1. Functional rescue assays were conducted by co-transfecting miR-214-3p with GPX4 to validate the regulatory relationship in vitro. EPB41L4A-AS1 was significantly downregulated in the serum of AIS patients, with lower levels predicting worse prognosis. Elevated EPB41L4A-AS1 expression substantially reduced pro-inflammatory markers (iNOS, TL-1β and TNF-α), but enhanced anti-inflammatory markers (Arg1 and IL-10) of OGD/R-injured BV2 cells. Meanwhile, the iron overload and lipid peroxidation in OGD/R cells were also improved. RIP, RNA pull-down, and luciferase reporter assays confirmed the specific binding of miR-214-3p to EPB41L4A-AS1 and GPX4. Upon EPB41L4A-AS1 overexpression, miR-214-3p mimic amplified the iron overload and oxidative stress and led to a pro-inflammatory state of BV2 cells under OGD/R conditions. Restoring GPX4 expression abrogated these observed effects. Lower serum EPB41L4A-AS1 correlates with poor prognosis in AIS patients. The mechanism underlying its neuroprotective effects against microglial state transition and ferroptosis was delineated through the miR-214-3p/GPX4 axis.

PMID:
42430067
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

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