Abstract
BackgroundParkinson disease (PD) is the most common movement disturbance characterized by the loss of dopaminergic (DA) neurons in midbrain. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is aberrantly expressed in neurons and is involved in the dendritic and synapse development. However, the role of MALAT1 and its underlying mechanism in PD remain to be defined.MethodsThe expressions of MALAT1 and miR-124 were evaluated by qRT-PCR. N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and SH-SY5Y cells subjected to N-methyl-4-phenylpyridinium (MPP+) were utilized to investigate the effect of MALAT1 on PD. TUNEL assay was performed to detect apoptosis of DA neurons in PD mice. Flow cytometry analysis was carried out to measure apoptosis of SH-SY5Y cells. Caspase3 activity and Cleaved Caspase3 expression were tested by caspase3 assay kit and western blot, respectively. TargetScan software and luciferase reporter assay were used to explore the relationship between MALAT1 and miR-124.ResultsMALAT1 was up-regulated and miR-124 was down-regulated in MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. MALAT1 knockdown attenuated MPTP-induced apoptosis of DA neurons in MPTP-induced PD mouse model. MALAT1 interacted with miR-124 to negatively regulate its expression. MALAT1 knockdown suppressed MPP+-induced apoptosis in SH-SY5Y cells, while miR-124 downregulation abrogated this effect. Moreover, MALAT1 knockdown improved miR-124 expression in MPTP/MPP+ induced models of PD.ConclusionsMALAT1 promotes the apoptosis by sponging miR-124 in mouse models of PD and in vitro model of PD, providing a potential theoretical foundation for the clinical application of MALAT1 against PD.
Highlights
Parkinson disease (PD) is the most common movement disturbance characterized by the loss of dopaminergic (DA) neurons in midbrain
Liu et al found that long non-coding RNAs (lncRNAs) Homeobox (HOX) transcript antisense RNA (HOTAIR) was highly expressed in the midbrain of PD mice induced by MPTP (N-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) and SH-SY5Y cells pre-treated with M PP+ (N-methyl-4-phenylpyridinium), and promoted the onset of PD induced by MPTP through regulating LPPK2 [9]
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was up‐regulated and miR‐124 was down‐regulated in MPTP‐induced PD mouse model and in MPP+‐intoxicated SH‐SY5Y cells Firstly, qRT-PCR was performed to determine the expressions of MALAT1 and miR-124 in the midbrain of MPTP-induced PD mouse model and M PP+-intoxicated SH-SY5Y cells
Summary
Parkinson disease (PD) is the most common movement disturbance characterized by the loss of dopaminergic (DA) neurons in midbrain. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is aberrantly expressed in neurons and is involved in the dendritic and synapse development. Liu et al found that lncRNA Homeobox (HOX) transcript antisense RNA (HOTAIR) was highly expressed in the midbrain of PD mice induced by MPTP (N-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) and SH-SY5Y cells pre-treated with M PP+ (N-methyl-4-phenylpyridinium), and promoted the onset of PD induced by MPTP through regulating LPPK2 (leucine-rich repeat kinase 2) [9]. MALAT1 was demonstrated to be aberrantly expressed in neurons and modulate a series of genes associated with the dendritic and synapse development [14, 15]. The exact role of MALAT1 and its underlying mechanism in PD has not been clearly established
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