LncRNA-T199678 Mitigates α-Synuclein-Induced Dopaminergic Neuron Injury via miR-101-3p

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by dopaminergic neuron death and the abnormal accumulation and aggregation of α-synuclein (α-Syn) in the substantia nigra (SN). Although the abnormal accumulation of α-Syn can solely promote and accelerate the progress of PD, the underlying molecular mechanisms remain unknown. Mounting evidence confirms that the abnormal expression of long non-coding RNA (lncRNA) plays an important role in PD. Our previous study found that exogenous α-Syn induced the downregulation of lncRNA-T199678 in SH-SY5Y cells via a gene microarray analysis. This finding suggested that lncRNA-T199678 might have a potential pathological role in the pathogenesis of PD. This study aimed to explore the influence of lncRNA-T199678 on α-Syn-induced dopaminergic neuron injury. Overexpression of lncRNA-T199678 ameliorated the neuron injury induced by α-Syn via regulating oxidative stress, cell cycle, and apoptosis. Studies indicate lncRNAs could regulate posttranscriptional gene expression via regulating the downstream microRNA (miRNA). To discover the downstream molecular target of lncRNA-T199678, the following experiment found out that miR-101-3p was a potential target for lncRNA-T199678. Further study showed that the upregulation of lncRNA-T199678 reduced α-Syn-induced neuronal damage through miR-101-3p in SH-SY5Y cells and lncRNA-T199678 was responsible for the α-Syn-induced intracellular oxidative stress, dysfunction of the cell cycle, and apoptosis. All in all, lncRNA-T199678 mitigated the α-Syn-induced dopaminergic neuron injury via targeting miR-101-3p, which contributed to promote PD. Our results highlighted the role of lncRNA-T199678 in mitigating dopaminergic neuron injury in PD and revealed a new molecular target for PD.

Commentary: LncRNA-T199678 Mitigates α-Synuclein-Induced Dopaminergic Neuron Injury via miR-101-3p

“…In this study, the result indicated that miR-101-3p was a potential downstream molecular target of lncRNA-T199678 (Bu et al, 2020b). Further investigation revealed that an overexpressed lncRNA-T199678 inhibited α-Syn-induced neuronal damage via regulating intracellular oxidative stress, cell cycle dysfunction, and apoptosis that was reversed by the miR-101-3p mimic (Figure 1) (Bu et al, 2020b). Therefore, an overexpressed lncRNA-T199678 ameliorated α-Syn-induced dopaminergic neuron injury by targeting miR-101-3p.…”

“…The striatum of patients with multiple system atrophy was observed to have an overexpressed miR-101 that was associated with α-Syn deposits, autophagy (Valera et al, 2017), inflammation (Han et al, 2019), oxidative stress, and apoptosis (Yi et al, 2019). In this study, the result indicated that miR-101-3p was a potential downstream molecular target of lncRNA-T199678 (Bu et al, 2020b). Further investigation revealed that an overexpressed lncRNA-T199678 inhibited α-Syn-induced neuronal damage via regulating intracellular oxidative stress, cell cycle dysfunction, and apoptosis that was reversed by the miR-101-3p mimic (Figure 1) (Bu et al, 2020b).…”

“…Previously, gene microarray analysis performed by Tao et al revealed decreased expression of lncRNA-T199678 in an exogenous α-Syn-induced SH-SY5Y cellular model of PD suggesting that it may be involved in dopaminergic neuron loss (Lin et al, 2018). In this study (Bu et al, 2020b), the function of lncRNA-T199678 in α-Syn-induced dopaminergic neuron injury was further investigated. Given that the localization of lncRNA in the cell is associated with its function, Tao et al first verified the presence of lncRNA-T199678 in the cytoplasm and a small amount in the nucleus of SH-SY5Y cells ( Figure 1) (Bu et al, 2020b).…”

“…In this study (Bu et al, 2020b), the function of lncRNA-T199678 in α-Syn-induced dopaminergic neuron injury was further investigated. Given that the localization of lncRNA in the cell is associated with its function, Tao et al first verified the presence of lncRNA-T199678 in the cytoplasm and a small amount in the nucleus of SH-SY5Y cells ( Figure 1) (Bu et al, 2020b). In order to examine the effect of lncRNA-T199678 on the α-Syn-mediated dopaminergic neuron injury, LncRNA-T199678 overexpression or silencing cell lines was constructed in the α-Syn-induced SH-SY5Y cellular model of PD.…”

“…In order to examine the effect of lncRNA-T199678 on the α-Syn-mediated dopaminergic neuron injury, LncRNA-T199678 overexpression or silencing cell lines was constructed in the α-Syn-induced SH-SY5Y cellular model of PD. Although the level of reactive oxygen species (ROS), the number of dividing cells, and the percentage of apoptotic cells, were significantly higher in the α-Syn-treated group and lncRNA-T199678 silencing groups, an overexpressed lncRNA-T199678 reversed intracellular oxidative stress, apoptosis, and abnormal cell cycle regulation indicating that it alleviated the damage from exogenous α-Syn (Bu et al, 2020b).…”