MicroRNA-31 inhibits traumatic brain injury-triggered neuronal cell apoptosis by regulating hypoxia-inducible factor-1A/vascular endothelial growth factor A axis.

Abstract

MicroRNAs are dysregulated in traumatic brain injury and are involved in neuronal cell behaviors. Previous studies identified miR-31 as a spinal cord injury-related microRNA, while its role in traumatic brain injury remains indistinct. Herein, we explored the participation of miR-31 in traumatic brain injury. Traumatic brain injury model was established after traumatic neuron injury. Neurocytes were transfected with miR-31 mimic or inhibitor. Cell counting kit-8, lactate dehydrogenase assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, and western blot were applied to examine cell viability, lactate dehydrogenase releasing, apoptosis, and apoptosis-related protein. The binding between miR-31 and hypoxia-inducible factor-1A was verified by luciferase assay. Quantitative reverse transcription-PCR was used to detect the regulation of traumatic neuron injury or hypoxia-inducible factor-1A overexpression on vascular endothelial growth factor A level. The effects of hypoxia-inducible factor-1A or vascular endothelial growth factor A on neuronal cell injury were examined. Additionally, phosphatidylinositol 3kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway was also examined using western blot. Downregulation of miR-31 promoted traumatic neuron injury-induced neuronal cell injury, and its overexpression did the opposite. Hypoxia-inducible factor-1A acted as a downstream mRNA of miR-31 and its downregulation was involved in miR-31-regulated neuronal cell injury. Vascular endothelial growth factor A level was elevated by traumatic neuron injury or hypoxia-inducible factor-1A overexpression. Hypoxia-inducible factor-1A enhanced neuronal cell injury via promoting vascular endothelial growth factor A expression. Furthermore, miR-31/hypoxia-inducible factor-1A/vascular endothelial growth factor A regulated PI3K/AKT/mTOR pathway in neuronal cells. Our study demonstrated miR-31 inhibited neuronal cell apoptosis via regulating hypoxia-inducible factor-1A/vascular endothelial growth factor A axis.

• Authors: Yan Qian, Xin Li, Raofei Fan, Qiaofen Li, Yang Zhang, Xiaona He, Wei Yang, Wei Sun, Shaokun Lv
• Journal: Neuroreport (Neuroreport) Vol. 33 Issue 1 Pg. 1-12 (01 05 2022) ISSN: 1473-558X [Electronic] England
• PMID: 34874324 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Hypoxia-Inducible Factor 1, alpha Subunit
• MicroRNAs
• Mirn31 microRNA, mouse
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse

Topics

• Animals
• Apoptosis (physiology)
• Brain Injuries, Traumatic (metabolism, pathology)
• Cells, Cultured
• Gene Expression Regulation (genetics)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Mice
• Mice, Inbred C57BL
• MicroRNAs (metabolism)
• Neurons (metabolism, pathology)
• Vascular Endothelial Growth Factor A (metabolism)