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循环长非编码 RNA 在帕金森病中的失调。

Dysregulation of Circulatory Levels of lncRNAs in Parkinson's Disease.

机构信息

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

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

出版信息

Mol Neurobiol. 2023 Jan;60(1):317-328. doi: 10.1007/s12035-022-03086-w. Epub 2022 Oct 20.

DOI:10.1007/s12035-022-03086-w
PMID:36264433
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.

摘要

越来越多的证据表明,长链非编码 RNA(lncRNA)参与了帕金森病(PD)的发病机制。在此,我们利用 GEO 数据库中的基因表达谱构建了一个 PD 特异性 ceRNA 网络。功能富集分析表明,ceRNA 网络可能参与了 PD 的发展。构建了 PPI 网络,并建立了基于五个枢纽基因的 ceRNA 子网络。在 32 名 PD 患者和 31 名健康对照者的队列中,进一步验证了 10 个差异表达的 lncRNA(TTC3-AS1、LINC01259、ZMYND10-AS1、CHRM3-AS1、MYO16-AS1、AGBL5-IT1、HOTAIRM1、RABGAP1L-IT1、HLCS-IT1 和 LINC00393)的表达。与微阵列数据一致,PD 患者的 LINC01259 表达明显低于对照组(P=0.008)。有趣的是,当根据性别将研究参与者分为男性和女性时,仅在男性患者和男性对照组中观察到这种差异(P=0.016)。然而,两组之间其他 lncRNA 的表达没有显著差异。受试者工作特征(ROC)曲线分析显示,LINC01259 对 PD 和早期 PD 的诊断能力分别为 0.694 和 0.677。GSEA 富集分析表明,LINC01259 主要富集在与免疫功能和炎症反应相关的生物学过程中。此外,LINC01259 的表达与患者的年龄、疾病持续时间、疾病阶段、MDS-UPDRS 评分、MDS-UPDRS III 评分、MMSE 评分和 MOCA 评分无关。本研究进一步证实了 lncRNA 在 PD 患者循环白细胞中的失调,表明 LINC01259 具有作为 PD 和早期 PD 诊断的新型免疫和炎症生物标志物的临床潜力。

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