LncRNA MEG8 ameliorates Parkinson's disease neuro-inflammation through miR-485-3p/FBXO45 axis
Xia Lin1, Taotao Tao1, Xinwei He1
1Department of Neurology, Taizhou Central Hospital (Taizhou University Hospital), No.999, Donghai Avenue, Jiaojiang District, Taizhou, 318000, Zhejiang, China.
Objective:
Studies suggest that LncRNA maternally expressed 8, small nucleolar RNA host gene (MEG8) contributes to inflammatory regulation, while the function and potential mechanisms of MEG8 in Parkinson's disease (PD) are unknown. This study aimed to assess the clinical value and biological function of MEG8 in PD.
Methods:
One hundred and two PD patients, eighty-six AD patients, and eighty healthy controls were enrolled in this study. Lipopolysaccharide (LPS)-induced microglia BV2 constructs an in vitro cell model. RT-qPCR was conducted to quantify the levels of MEG8, miR-485-3p, and FBXO45 in serum and cells. ROC curve was employed to examine the diagnostic value of MEG8 in PD. Serum and cellular pro-inflammatory factor secretion were quantified by ELISA. Dual-luciferase reporter and RIP assay to validate the targeting relationship between miR-485-3p and FBXO45.
Results:
MEG8 and FBXO45 were significantly decreased in the serum of PD patients and LPS-induced bv2, while miR-485-3p was increased (P < 0.05). ROC curve confirmed that serum MEG8 has high sensitivity and specificity to identify PD patients from healthy controls and AD patients, respectively. Elevated MEG8 alleviated LPS-induced inflammatory factor overproduction compared with LPS-induced BV2 (P < 0.05), but this alleviating effect was eliminated by miR-485-3p (P < 0.05). The LPS-induced inflammatory response was suppressed by the low expression of miR-485-3p but significantly reversed by silencing of FBXO45. MEG8 was a sponge for miR-485-3p and inhibited its levels and promoted FBXO45 expression (P < 0.05).
Conclusion:
Elevated MEG8 is a potential diagnostic biomarker for PD and may mitigate inflammatory damage in PD via the miR-485-3p/FBXO45 axis.
Insights
Long non-coding RNA maternally expressed 8 (MEG8) shows potential as a diagnostic biomarker for Parkinson's disease (PD). Elevated MEG8 may reduce inflammation in PD by regulating the miR-485-3p/FBXO45 pathway.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Long non-coding RNA maternally expressed 8 (MEG8) is implicated in inflammatory regulation.
- The role and mechanisms of MEG8 in Parkinson's disease (PD) remain uncharacterized.
- This study investigates the clinical significance and biological function of MEG8 in PD.
Purpose of the Study:
- To evaluate MEG8 as a diagnostic biomarker for Parkinson's disease (PD).
- To elucidate the biological function and underlying mechanisms of MEG8 in PD pathogenesis.
- To explore the potential of MEG8 in mitigating inflammatory responses associated with PD.
Main Methods:
- Serum and cellular levels of MEG8, miR-485-3p, and FBXO45 were quantified using RT-qPCR in 102 PD patients, 86 AD patients, and 80 healthy controls.
- An in vitro model of LPS-induced microglia BV2 cells was utilized to study inflammatory responses.
- Diagnostic value was assessed via ROC curve analysis, and targeting relationships were validated using dual-luciferase reporter and RIP assays.
Main Results:
- MEG8 and FBXO45 levels were significantly decreased in PD patients and LPS-treated BV2 cells, while miR-485-3p levels were elevated.
- Serum MEG8 demonstrated high sensitivity and specificity for distinguishing PD patients from healthy and AD controls.
- MEG8 alleviated LPS-induced inflammation, an effect dependent on the miR-485-3p/FBXO45 axis, where MEG8 acts as a sponge for miR-485-3p, inhibiting it and promoting FBXO45 expression.
Conclusions:
- Elevated MEG8 serves as a potential diagnostic biomarker for Parkinson's disease (PD).
- MEG8 may exert anti-inflammatory effects in PD through the miR-485-3p/FBXO45 pathway.
- The findings highlight a novel molecular mechanism involving MEG8 in PD pathophysiology.
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