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ACS Chem Neurosci. 2019 May 15;10(5):2243-2249. doi: 10.1021/acschemneuro.8b00460. Epub 2019 Apr 1.

Altered Expression Levels of MicroRNA-132 and Nurr1 in Peripheral Blood of Parkinson's Disease: Potential Disease Biomarkers.

Yang Z1,2,3, Li T2,3, Li S2,3, Wei M2,3, Qi H2,3, Shen B4, Chang RC5, Le W2,3, Piao F1.

Author information

1
Department of Occupational and Environmental Health , Dalian Medical University , Dalian 116044 , China.
2
Center for Clinical Research on Neurological Diseases, the First Affiliated Hospital , Dalian Medical University , Dalian 116021 , China.
3
Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, the First Affiliated Hospital , Dalian Medical University , Dalian 116021 , China.
4
Institute for Systems Genetics, West China Hospital , Sichuan University , Chengdu 610041 , China.
5
Laboratory of Neurodegenerative Diseases, LKS Faculty of Medicine, School of Biomedical Sciences , The University of Hong Kong , Hong Kong , China.

Abstract

MicroRNAs (miRNAs) are small and evolutionary conserved noncoding RNAs that are involved in post-transcriptional gene regulation. Differential expression levels of miRNAs can be used as potential biomarkers of disease. Previous animal studies have indicated that the expression level of miR-132 is negatively correlated with its downstream molecule nuclear receptor related 1 protein (Nurr1), which is one of the key factors for the maintenance of dopaminergic function and is particularly vulnerable in Parkinson's disease (PD). However, this correlation has not been confirmed in human patients with PD. Moreover, the possible involvement of miR-132 during the pathogenesis and progression of PD is not fully investigated. Therefore, in the present study, we determined the peripheral circulation levels of miR-132 and Nurr1 in patients with PD, neurological disease controls (NDC) and healthy controls (HC) by reverse transcription real-time quantitative PCR (RT-qPCR). Our data clearly demonstrated that the plasma miR-132 level in PD was significantly higher than those in HC (178%, p < 0.05) and NDC (188%, p < 0.001). When adjusted for gender and age, higher level of miR-132 expression was associated with the significantly increased risk for PD in males and was closely related with the disease stages and disease severity. Furthermore, peripheral Nurr1 was significantly decreased in PD compared with HC (56%, p < 0.001) and NDC (58%, p < 0.001). Much more interestingly, further analysis revealed a negative correlation between the decreased Nurr1 level and the elevated miR-132 level in PD. All these findings indicated that the combination of a high miR-132 level with the low level of its downstream Nurr1 might be a potential biomarker aiding in the diagnosis of PD and monitoring disease progression.

KEYWORDS:

Nurr1; Parkinson’s disease; biomarker; miR-132; peripheral blood

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