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Dysregulation of Circulatory Levels of lncRNAs in Parkinson’s Disease

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Abstract 

Emerging evidence suggested that long non-coding RNAs (lncRNAs) were involved in Parkinson’s disease (PD) pathogenesis. Herein, we used gene expression profiles from GEO database to construct a PD-specific ceRNA network. Functional enrichment analysis suggested that ceRNA network might participate in the development of PD. PPI networks were constructed, and the ceRNA subnetwork based on five hub genes was set up. In a cohort of 32 PD patients and 31 healthy controls, the expression of 10 DElncRNAs (TTC3-AS1, LINC01259, ZMYND10-AS1, CHRM3-AS1, MYO16-AS1, AGBL5-IT1, HOTAIRM1, RABGAP1L-IT1, HLCS-IT1, and LINC00393) were further verified. Consistent with the microarray data, LINC01259 expression was significantly lower in PD patients compared with controls (P = 0.008). Intriguingly, such a difference was only observed among male patients and male controls when dividing study participants based on their gender (P = 0.016). However, the expression of other lncRNAs did not differ significantly between the two groups. Receiver operating characteristic (ROC) curve analysis revealed that the diagnostic power of LINC01259 was 0.694 for PD and 0.677 for early-stage PD. GSEA enrichment analysis revealed that LINC01259 was mainly enriched in biological processes associated with immune function and inflammatory response. Moreover, LINC01259 expression was not correlated with age of patients, disease duration, disease stage, MDS-UPDRS score, MDS-UPDRS III score, MMSE score, and MOCA score. The current study provides further evidence for the dysregulation of lncRNAs in circulating leukocytes of PD patients, revealing that LINC01259 has clinical potential as a novel immune and inflammatory biomarker for PD and early-stage PD diagnosis.

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All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Acknowledgements

We would like to thank Dr. Jiahang Song and Dr. Yifang Hu for the experimental guidance and useful discussion of the work.

Funding

This work was supported by the Natural Science Foundation of Jiangsu Province (BK20201117) and the National Science and Technology Innovation 2030: Major program of “Brain Science and Brain-Inspired Intelligence Research” (2021ZD0201807).

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  1. Jin-Ying Zhao, Rong-Rong Pan, and Teng Jiang contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210000, China

    Ting Huang, Jin-Ying Zhao, Rong-Rong Pan, Teng Jiang, Qing Huang, Xi-Xi Wang, Peng-Yu Gong, You-Yong Tian & Ying-Dong Zhang

  2. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 210000, China

    Xin-Xin Fu

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Contributions

Study design and manuscript draft: YDZ, YYT, and TH; experiment implementation: TH, JYZ, RRP, and TJ; data collection: XXF, QH, XXW, and PYG. All authors have read and approved the final manuscript.

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Correspondence to You-Yong Tian or Ying-Dong Zhang.

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Huang, T., Zhao, JY., Pan, RR. et al. Dysregulation of Circulatory Levels of lncRNAs in Parkinson’s Disease. Mol Neurobiol 60, 317–328 (2023). https://doi.org/10.1007/s12035-022-03086-w

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