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

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-kappa B and NLRP3 inflammasome. Meanwhile, bioinformatics analysis and dual-luciferase reporter assay were utilized to confirm the targeting relationships among miR-1243p, 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-kappa B and NLRP3 inflammasome, while inhibiting NF-KB 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-kappa B axis.

Automated summary

The study reveals that HOXA11-AS plays a role in promoting inflammation in Parkinson's disease, leading to neuronal damage and microglia activation. Conversely, miR-124-3p has opposite effects by inhibiting inflammation. By modulating the interactions among these molecules, the neurological damages caused by PD can be alleviated.