Profiling of Differentially Expressed MicroRNAs in Saliva of Parkinson's Disease Patients

Abstract

Objective: This study aims to identify differentially expressed salivary miRNAs and validate the diagnostic potential for idiopathic Parkinson's disease (PD). Also, the disease specificity of candidate miRNAs was evaluated between PD, multiple system atrophy (MSA), and essential tremor (ET).Methods: We collected salivary samples from 50 PD, 20 ET, and 20 MSA patients, as well as 30 healthy controls (HCs). In the discovery phase, salivary miRNA microarray analysis was performed. In-silico analysis was used to investigate the target genes of differentially expressed miRNAs and clustered pathways. In validation phase, RT-qPCR was performed with samples from 30 PD patients and 30 HCs. Subsequently, we investigated candidate miRNAs in all recruited subjects. Receiver operating characteristic curve and Spearman correlation analysis was performed to determine diagnostic usefulness.Results: We identified 43 miRNAs that were differentially expressed between 5 PD patients and 5 HCs by miRNA microarray analysis. Computational analysis revealed the target genes were clustered in the pathways associated with ubiquitin protein ligase activity. The result of RT-qPCR showed that the miR-29a-3p and miR-29c-3p were found to be significantly downregulated (p = 0.004, p = 0.027), whereas the miR-6756-5p was significantly upregulated in 30 PD patients compared with 30 HCs (p = 0.032). The miR-29a-3p expression level in PD patients was significantly lower than ET patients (p = 0.035), but higher than MSA patients (p < 0.0001). The diagnostic efficacy reached a little higher when the combination of miR-29a-3p and miR-29c-3p.Conclusion: The miRNA combination of salivary miR-29a-3p and miR-29c-3p has potential to be a diagnostic biomarker for idiopathic PD.

Diagnostic Value of Salivary Real‐Time Quaking‐Induced Conversion in Parkinson's Disease and Multiple System Atrophy

“…Recent studies indicated that salivary microRNAs could serve as potential biomarkers in the diagnosis of PD. 15,16 Apart from noncoding RNA, salivary oligomeric α-syn also showed high potential in the diagnosis of PD. 9,17 Remarkably, the oligomeric α-syn levels and the oligomeric α-syn/total α-syn ratio were increased significantly in the extracellular vesicles of patients with PD compared with healthy control subjects.…”

“…Some achievements have been made in the studies of saliva as a noninvasive and easily accessible biospecimen in PD biomarker discovery. Recent studies indicated that salivary microRNAs could serve as potential biomarkers in the diagnosis of PD 15,16 . Apart from noncoding RNA, salivary oligomeric α‐syn also showed high potential in the diagnosis of PD 9,17 .…”

Epigenetic Changes in Prion and Prion-like Neurodegenerative Diseases: Recent Advances, Potential as Biomarkers, and Future Perspectives

“…Comparing the different profiles, only one miRNA, miR-324-3p, is commonly downregulated in the brain, body fluids, and EVs of AD patients, but its expression is not altered in AD mouse models. MiRNA profiles have been also characterized in brain [ 126 , 127 , 128 , 129 ], gut [ 130 ], blood [ 128 ], plasma [ 131 , 132 ], serum [ 133 ], CSF [ 134 , 135 ], saliva [ 136 ], and EVs [ 131 , 137 ] of PD patients; in brain of a PD mouse model [ 135 ]; in blood of a PD rat model [ 138 ]; and in a PD in vitro model [ 139 ]. Although no common miRNAs are found when comparing all the above-mentioned PD profiles, there are common miRNAs between some tissues and body fluids.…”

“…The following supporting information can be downloaded at: . References [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 ,…”

Confounding Factors Impacting microRNA Expression in Human Saliva: Methodological and Biological Considerations

“…Notably, high powered cohort studies identify predictive miRNAs for of autism spectrum disorder [ 4 , 16 , 17 ], traumatic brain injury [ 18 , 19 , 20 , 21 ] endometriosis [ 22 ], and a variety of cancers [ 23 , 24 , 25 ]. Other recent studies include the prediction of alcohol use disorder [ 26 , 27 ], Parkinson’s Disease [ 28 , 29 ], and malignant pleural effusion [ 30 ]. Broad commonalities of these studies include saliva collection, saliva storage, miRNA extraction and isolation, and miRNA expression profiling.…”