Research Paper Volume 16, Issue 3 pp 2828—2847

MicroRNA-124 negatively regulates STAT3 to alleviate hypoxic-ischemic brain damage by inhibiting oxidative stress

Jiaqing Geng1,2, *, , Jiangpeng Feng3, *, , Fangzi Ke1, , Fang Fang1, , Xiaoqi Jing1, , Jiaxin Tang1, , Chengzhi Fang1, , Binghong Zhang1, ,

  • 1 Departments of Neonatology, Renmin Hospital of Wuhan University, Wuhan 430062, China
  • 2 Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430062, China
  • 3 State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430062, China
* Equal contribution

Received: October 10, 2023       Accepted: December 29, 2023       Published: February 5, 2024
How to Cite

Copyright: © 2024 Geng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


MicroRNA-124 (miR-124) is implicated in various neurological diseases; however, its significance in hypoxic-ischaemic brain damage (HIBD) remains unclear. This study aimed to elucidate the underlying pathophysiological mechanisms of miR-124 in HIBD. In our study performed on oxygen-glucose deprivation followed by reperfusion (OGD)/R-induced primary cortical neurons, a substantial reduction in miR-124 was observed. Furthermore, the upregulation of miR-124 significantly mitigated oxidative stress, apoptosis, and mitochondrial impairment. We demonstrated that miR-124 interacts with the signal transducer and activator of transcription 3 (STAT3) to exert its biological function using the dual-luciferase reporter gene assay. As the duration of OGD increased, miR-124 exhibited a negative correlation with STAT3. STAT3 overexpression notably attenuated the protective effects of miR-124 mimics, while knockdown of STAT3 reversed the adverse effects of the miR-124 inhibitor. Subsequently, we conducted an HIBD model in rats. In vivo experiments, miR-124 overexpression attenuated cerebral infarction volume, cerebral edema, apoptosis, oxidative stress, and improved neurological function recovery in HIBD rats. In summary, the neuroprotective effects of the miR-124/STAT3 axis were confirmed in the HIBD model. MiR-124 may serve as a potential biomarker with significant therapeutic implications for HIBD.


HIBD: hypoxic–ischaemic brain injury; HIE: hypoxic–ischaemic encephalopathy; miRNAs: microRNAs; CREB: cyclic AMP-responsive element binding protein; TLR4: toll-like receptor 4; STAT3: transducer and activator of transcription 3; SD: Sprague-Dawley; NC: negative control; TTC: 2,3,5-triphenyltetrazolium chloride; H&E: hematoxylin–eosin; IHC: immunohistochemistry; OGD/R: oxygen-glucose deprivation/reperfusion; CCK-8: Cell Counting Kit 8; cDNA: complementary DNA; NC: nitrocellulose; DCFH-DA: 2’-7’dichlorofluorescin diacetate; ROS: reactive oxygen species; MDA: malondialdehyde; 8-OHdG: 8-hydroxydeoxyguanosine; Mito-Tracker: mitochondria tracker; SOD: superoxide dismutase.