Abstract
The molecular mechanism underlying Parkinson’s disease (PD), an increasingly common neurodegenerative disease, remains unclear. Long non-coding RNA (lncRNA) plays essential roles in gene expression and human diseases. We hypothesize that lncRNAs are involved in neuronal degeneration of PD. Using microarray, we identified 122 differentially expressed (DE) lncRNAs and 48 DE mRNAs between the circulating leukocytes from PD patients and healthy controls. There were 714 significant correlations (r ≥ 0.8 or ≤−0.8, p < 0.05) among the DE lncRNAs and mRNAs. Gene function and pathway analysis of the 48 DE mRNAs revealed biological pathways related to PD pathogenesis, including immune response, inflammatory response, MAPK, and Jak-STAT pathway. In a cohort of 72 PD patients and 22 healthy controls, the upregulation of four lncRNAs (AC131056.3-001, HOTAIRM1, lnc-MOK-6:1, and RF01976.1-201) in circulating leukocytes of PD patients were further confirmed. These lncRNAs were also upregulated in THP-1 cells, a human monocytic cell line, after inflammatory stimulation. Interestingly, the conditioned culture medium of THP-1 cells or 6-OHDA significantly increased the expression of these lncRNAs in SH-SY5Y cells, a human neuroblastoma cell line expressing dopaminergic markers. Importantly, overexpression of AC131056.3-001 or HOTAIRM1 increased baseline and 6-OHDA-induced apoptosis of SH-SY5Y cells. Taken together, we identified distinct expression profiles of lncRNA and mRNA in circulating leukocytes between PD patients and healthy controls. Dysregulated lncRNAs such as HOTAIRM1 and AC131056.3-001 may contribute to PD pathogenesis by promoting the apoptosis of dopaminergic neuron.
Highlights
Parkinson’s disease is the most common neurodegenerative movement disorder affecting approximately 2% of people in the world (Wirdefeldt et al, 2011)
We identified 122 differentially expressed (DE) long non-coding RNA (lncRNA) in circulating leukocytes of Parkinson’s disease (PD) patients compared to healthy controls
We demonstrated that there were distinct lncRNA and mRNA expression profiles in the circulating leukocytes between PD patients and healthy controls
Summary
Parkinson’s disease is the most common neurodegenerative movement disorder affecting approximately 2% of people in the world (Wirdefeldt et al, 2011). Neuroinflammation, mitochondrial dysfunction, oxidative stress, and alterations of the human microbiome have been implicated in the pathogenesis of PD (Olanow, 2007; Sampson et al, 2016). LncRNAs have been reported to play critical roles in gene expression, gene imprinting, chromosome conformation, cell differentiation, cell cycle, and apoptosis (Ponting et al, 2009; Rinn and Chang, 2012). Aberrant lncRNAs expression profiles were reported in human disease (Batista and Chang, 2013), including cancer (DasGupta et al, 2017), cardiovascular disorders (Bar et al, 2016), and diabetes mellitus (Knoll et al, 2015)
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