miR-7a-5p attenuates hypoxic-ischemic encephalopathy by suppressing PARP1-mediated parthanatos
Abstract
Hypoxic-ischemic encephalopathy (HIE) causes severe neonatal brain injury, with PARP1 hyperactivation implicated in neuronal death. Using a rat HIE model and glutamate-exposed HT22 neurons, we found that miR-7a-5p is significantly downregulated in both peripheral blood and the injured cortex of HIE rats. PARP1 hyperactivation triggered parthanatos, characterized by PAR polymer accumulation and apoptosis-inducing factor (AIF) nuclear translocation, without activating caspase-dependent apoptosis. Luciferase assays confirmed direct targeting of miR-7a-5p to the 3′ UTR of PARP1, suppressing its expression. Exogenous miR-7a-5p reduces infarction volume, improves neural morphology, and preserves neurological function recovery in HIE rats. In vitro, miR-7a-5p overexpression or pharmacological PARP1 inhibition attenuated glutamate-induced neuronal death, mitochondrial membrane potential (MMP) loss, ROS overproduction, and PAR/AIF dysregulation. Crucially, PARP1 agonist MNNG reversed miR-7a-5p-mediated neuroprotection, establishing the indispensability of the miR-7a-5p/PARP1 axis. miR-7a-5p is a key regulator of parthanatos, suppressing PARP1 hyperactivation, mitigating mitochondrial dysfunction, and offering a therapeutic target for HIE.
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BibTeX
@article{chen2026mir7a5p,
title = {{miR-7a-5p attenuates hypoxic-ischemic encephalopathy by suppressing PARP1-mediated parthanatos}},
author = {Danmei Chen and Xiangyu Kong and Hequan Zhong and Yunpeng Zhang and Chenqin Si and Ayipaxiaguli Kasimu and Rui Qiao and Yuting Song and Bing Li},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117947},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03330-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - miR-7a-5p attenuates hypoxic-ischemic encephalopathy by suppressing PARP1-mediated parthanatos
AU - Danmei Chen
AU - Xiangyu Kong
AU - Hequan Zhong
AU - Yunpeng Zhang
AU - Chenqin Si
AU - Ayipaxiaguli Kasimu
AU - Rui Qiao
AU - Yuting Song
AU - Bing Li
PY - 2026
DA - 2026/10/26
JO - iScience
DO - 10.1016/j.isci.2026.117947
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03330-4
AB - Hypoxic-ischemic encephalopathy (HIE) causes severe neonatal brain injury, with PARP1 hyperactivation implicated in neuronal death. Using a rat HIE model and glutamate-exposed HT22 neurons, we found that miR-7a-5p is significantly downregulated in both peripheral blood and the injured cortex of HIE rats. PARP1 hyperactivation triggered parthanatos, characterized by PAR polymer accumulation and apoptosis-inducing factor (AIF) nuclear translocation, without activating caspase-dependent apoptosis. Luciferase assays confirmed direct targeting of miR-7a-5p to the 3′ UTR of PARP1, suppressing its expression. Exogenous miR-7a-5p reduces infarction volume, improves neural morphology, and preserves neurological function recovery in HIE rats. In vitro, miR-7a-5p overexpression or pharmacological PARP1 inhibition attenuated glutamate-induced neuronal death, mitochondrial membrane potential (MMP) loss, ROS overproduction, and PAR/AIF dysregulation. Crucially, PARP1 agonist MNNG reversed miR-7a-5p-mediated neuroprotection, establishing the indispensability of the miR-7a-5p/PARP1 axis. miR-7a-5p is a key regulator of parthanatos, suppressing PARP1 hyperactivation, mitigating mitochondrial dysfunction, and offering a therapeutic target for HIE.
SN - 2589-0042
ER -