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Background <p>Increasing evidence has highlighted the crucial role of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the development and progression of Parkinson’s disease (PD). Investigating which lncRNA and mRNA biomarkers are associated with PD rehabilitation is valuable.</p> Methods <p>Six patients with PD (PWP, Hoehn &amp; Yahr stages 1.5–2.5) and age- and sex-matched healthy controls (HCs) were recruited. Total RNA was extracted from extracellular vesicles (EVs) from peripheral blood samples collected before and after 14 days of rehabilitation in the hospital. Differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were identified via next-generation sequencing (NGS), and a coexpression network was constructed.</p> Results <p>Overall, 3038 DEmRNAs (2337 upregulated/701 downregulated) and 1723 DElncRNAs (1278 upregulated/445 downregulated) were identified between prerehabilitation (prerehab) PWPs and HCs, whereas 3117 DEmRNAs (2490 upregulated/629 downregulated) and 1931 DElncRNAs (1561 upregulated/370 downregulated) were identified between postrehabilitation (postrehab) PWPs and HCs. Moreover, 1662 DEmRNAs (606 upregulated/1056 downregulated) and 1729 DElncRNAs (593 upregulated/1136 downregulated) were identified between prerehab PWPs and postrehab PWPs. Four DEmRNAs and 19 DElncRNAs were found in the blood EVs of both pre- and postrehab PWPs. GO and KEGG enrichment analyses revealed significant enrichment of the DEGs associated with the apoptotic process, mitogen-activated protein kinase (MAPK) signaling pathway, and Wnt signaling pathway. Coexpression network analysis revealed one DEmRNA (ENSG00000168646, AXIN2) and one positively related DElncRNA (ENST00000577329). The expression of the DEGs was validated in human samples via quantitative reverse transcription polymerase chain reaction (qRT‒PCR).</p> Conclusions <p>These findings suggest that the apoptotic pathway-related biomarker AXIN2 may be involved in PD rehabilitation, which should be further confirmed in clinical evaluations after PD rehabilitation.</p>

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Integrative analysis of mRNA and LncRNA profiles from small extracellular vesicles identifies apoptosis-related biomarkers in patients with Parkinson’s disease after rehabilitation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月28日

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  • Yixuan Wang,
  • Yonghong Liu,
  • Boyan Fang,
  • Cui Liu,
  • Keke Chen,
  • Detao Meng,
  • Zhaohui Jin

摘要

Background

Increasing evidence has highlighted the crucial role of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the development and progression of Parkinson’s disease (PD). Investigating which lncRNA and mRNA biomarkers are associated with PD rehabilitation is valuable.

Methods

Six patients with PD (PWP, Hoehn & Yahr stages 1.5–2.5) and age- and sex-matched healthy controls (HCs) were recruited. Total RNA was extracted from extracellular vesicles (EVs) from peripheral blood samples collected before and after 14 days of rehabilitation in the hospital. Differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were identified via next-generation sequencing (NGS), and a coexpression network was constructed.

Results

Overall, 3038 DEmRNAs (2337 upregulated/701 downregulated) and 1723 DElncRNAs (1278 upregulated/445 downregulated) were identified between prerehabilitation (prerehab) PWPs and HCs, whereas 3117 DEmRNAs (2490 upregulated/629 downregulated) and 1931 DElncRNAs (1561 upregulated/370 downregulated) were identified between postrehabilitation (postrehab) PWPs and HCs. Moreover, 1662 DEmRNAs (606 upregulated/1056 downregulated) and 1729 DElncRNAs (593 upregulated/1136 downregulated) were identified between prerehab PWPs and postrehab PWPs. Four DEmRNAs and 19 DElncRNAs were found in the blood EVs of both pre- and postrehab PWPs. GO and KEGG enrichment analyses revealed significant enrichment of the DEGs associated with the apoptotic process, mitogen-activated protein kinase (MAPK) signaling pathway, and Wnt signaling pathway. Coexpression network analysis revealed one DEmRNA (ENSG00000168646, AXIN2) and one positively related DElncRNA (ENST00000577329). The expression of the DEGs was validated in human samples via quantitative reverse transcription polymerase chain reaction (qRT‒PCR).

Conclusions

These findings suggest that the apoptotic pathway-related biomarker AXIN2 may be involved in PD rehabilitation, which should be further confirmed in clinical evaluations after PD rehabilitation.