1.Differential expression of circulating miRNAs in Parkinson’s disease patients: Potential early biomarker?
Siti Aishah Sulaiman ; Nor Ilham Ainaa Muhsin ; Ahmad Rasyadan Arshad ; Wan Fahmi Wan Mohamad Nazarie ; Rahman Jamal ; Norlinah Mohamed Ibrahim ; Nor Azian Abdul Murad
Neurology Asia 2020;25(3):319-329
Background & Objective: Circulating microRNAs (miRNAs) expressions have been suggested as
potential biomarkers for Parkinson’s Disease (PD). Identification of early biomarkers for PD is
important and crucial as PD symptoms occur at a late stage. Hence, these biomarkers could be used
in molecular diagnosis for early detection. We therefore examined and compared the expression of
circulating miRNAs between PD patients and controls. We also compared the miRNAs expression
between early-onset PD (EOPD) and late-onset PD (LOPD). Methods: RNA was extracted from
the plasma of EOPD (onset age <50 years; n=14), LOPD (onset age < 60 years; n=14) and healthy
controls (n=11). The miRNAs expression was determined using the Affymetrix GeneChip microarray.
Differential analysis was performed using the R software. Significantly differentiated miRNAs were
subsequently analyzed for functional enrichment and biological pathway using the FunRich v1.3
software based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The Omics.net
was used to determine the predicted target mRNAs of these miRNAs, and their interactions, based
on the five most differentially expressed miRNAs. Results: In total, 273 miRNAs were upregulated
in PD patients compared to controls. The most significant miRNAs were hsa-miR-301a-3p, 100-5p,
140-5p, 486-3p, 143-3p (fold change ranging from 11.2 – 32.0). A total of 140 circulating miRNAs
were differentially expressed in EOPD compared to LOPD. Five of these miRNAs (one upregulated
miRNA (hsa-miR-29b-3p) and four downregulated miRNAs (hsa-miR-297, 4462, 1909-5p and 346)
belonged exclusively to the EOPD patients. The predicted gene targets of these miRNAs involved in
dopaminergic synapse regulation, crucial to the pathogenesis of PD.
Conclusion: Circulating miRNAs differ between PD patients and controls, and between EOPD and
LOPD patients. A validation study with a larger and more diverse multi-ethnic population should be
conducted to confirm our results.