Research Paper Volume 13, Issue 8 pp 11455—11469
Inhibition of long non-coding RNA HOXA11-AS against neuroinflammation in Parkinson's disease model via targeting miR-124-3p mediated FSTL1/NF-κB axis
- 1 Department of Neurology, Kaifeng Central Hospital, Kaifeng 475000, Henan, China
Received: May 2, 2020 Accepted: December 18, 2020 Published: April 4, 2021https://doi.org/10.18632/aging.202837
How to Cite
Copyright: © 2021 Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Studies have revealed that lncRNA HOXA11-AS contributes to regulating inflammation, while the role of HOXA11-AS in Parkinson’s disease (PD) remains unclear.
Methods: Both in vivo and in vitro PD models were induced. Gain- or loss-assays of HOXA11-AS and miR-124-3p were conducted. The neurological functions, dopaminergic neurons damage, microglia activation of PD mice were measured. Afterwards, the expressions of inflammatory factors were examined with RT-PCR. Western blot was employed to detect the level of FSTL1, NF-κB and NLRP3 inflammasome. Meanwhile, bioinformatics analysis and dual-luciferase reporter assay were utilized to confirm the targeting relationships among miR-124-3p, HOXA11-AS and FSTL1.
Results: HOXA11-AS promoted MPTP-mediated SH-SY5Y neuronal injury and LPS-induced microglia activation, while miR-124-3p had the opposite effects. Additionally, miR-124-3p was the target of HOXA11-AS and FSTL1. HOXA11-AS overexpression enhanced the expression of inflammatory factors and FSTL1, NF-κB and NLRP3 inflammasome, while inhibiting NF-κB weakened HOXA11-AS-mediated neuronal damage and microglia activation. Moreover, HOXA11-AS1 downregulation ameliorated MPTP-induced neurological damages and neuroinflammation in mice.
Conclusion: Inhibition of HOXA11-AS protects mice against PD through repressing neuroinflammation and neuronal apoptosis through miR-124-3p-FSTL1-NF-κB axis.
PD: Parkinson's disease; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; LPS: lipopolysaccharide; TH: Tyrosine Hydroxylase; AD: Alzheimer's disease; NMS: non-motor symptoms; L-DOPA: levodopa; lncRNAs: long non-coding RNAs; CNS: central nervous system; SNCA: upregulating α-synuclein; miRNAs: MicroRNAs; SCIRI: spinal cord ischemia-reperfusion injury; SN: substantia nigra.