The MicroRNA-224 Inhibitor Prevents Neuronal Apoptosis via Targeting Spastic Paraplegia 7 After Cerebral Ischemia.

Abstract

Recently, the study of microRNA expression profile has shown that miR-224 was implicated in neuron injury, but the mechanism of miR-224 on regulating neuronal apoptosis is completely unclear until now. Therefore, the current study aims to illuminate the miR-224 and its target gene on the modulation of neuronal cell apoptosis induced by ischemic injury. In this study, we used oxygen/glucose deprivation (OGD)-induced human-derived HCN-2 cells to establish the model of cerebral ischemia injury. We found that miR-224 was upregulated in injured cells (human brain cortical neuron). Using bioinformatics analyses, we found that miR-224 targeted the 3'UTR of spastic paraplegia 7 (SPG7) and the miR-224 inhibitor promoted expression of SPG7 and promoter activity of SPG7 3'UTR. In addition, we further found that miR-224 inhibitor enhanced interaction SPG7 with mitochondrial voltage-dependent anion channel (VDAC1) detected by co-immunoprecipitation in injured cells. The knockdown of SPG7 reduced mitochondrial membrane potential and caused higher mitochondrial calcium retention in injured cells. Knockdown of SPG7 inhibits expression of nicotinic acetylcholine receptor. Besides, the miR-224 inhibitor reduced neuronal cell apoptosis was increased by knockdown of either SPG7 or VDAC1. Overall, miR-224 inhibitor may prevent neuronal cell apoptosis by targeting SPG7 3'UTR and promote interaction SPG7 with VDAC1 after cerebral ischemia. Downregulation of SPG7 induces VDAC1 to form mitochondria permeability transition pore probably by inhibiting expression of nicotinic acetylcholine receptor, resulting in mitochondrial membrane depolarization and higher mitochondrial calcium retention.

• Authors: Feng Fu, Dingfeng Wu, Chao Qian
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 59 Issue 3 Pg. 421-9 (Jul 2016) ISSN: 1559-1166 [Electronic] United States
• PMID: 27165196 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• MIRN224 microRNA, human
• MicroRNAs
• VDAC1 protein, human
• Voltage-Dependent Anion Channel 1
• Metalloendopeptidases
• SPG7 protein, human
• ATPases Associated with Diverse Cellular Activities
• Glucose
• Oxygen
• Calcium

Topics

• 3' Untranslated Regions
• ATPases Associated with Diverse Cellular Activities
• Apoptosis
• Calcium (metabolism)
• Cell Hypoxia
• Cell Line
• Glucose (deficiency)
• Humans
• Membrane Potential, Mitochondrial
• Metalloendopeptidases (genetics, metabolism)
• MicroRNAs (genetics, metabolism)
• Neurons (metabolism)
• Oxygen (metabolism)
• Voltage-Dependent Anion Channel 1 (metabolism)