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LncRNA MEG8 ameliorates Parkinson’s disease neuro-inflammation through miR-485-3p/FBXO45 axis

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Abstract

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.

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The data used and analyzed can be obtained from the corresponding author under a reasonable request.

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Acknowledgements

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Funding

This study was funded by the Taizhou Social Development Science and Technology Plan Project (22ywb37).

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Contributions

XL carried out the research design and conception; TT and XH analyzed and interpreted the data regarding; LM performed the examination of sample; LP and TT contributed essential reagents or tools; XL and LC authors wrote and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Linkao Chen.

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The authors declare that they have no competing interests.

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The experimental procedures were all in accordance with the guideline of the Ethics Committee of Taizhou Central Hospital (Taizhou University Hospital) and has approved by the Ethics Committee of Taizhou Central Hospital (Taizhou University Hospital). This study complies with the Declaration of Helsinki. A signed written informed consent was obtained from each patient.

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Lin, X., Tao, T., He, X. et al. LncRNA MEG8 ameliorates Parkinson’s disease neuro-inflammation through miR-485-3p/FBXO45 axis. Acta Neurol Belg 124, 549–557 (2024). https://doi.org/10.1007/s13760-023-02388-7

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  • DOI: https://doi.org/10.1007/s13760-023-02388-7

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