LncRNA RMST Regulates Neuronal Apoptosis and Inflammatory Response via Sponging miR-150-5p in Parkinson’s Disease

Abstract

<b><i>Introduction:</i></b> LncRNA rhabdomyosarcoma 2-associated transcript (RMST) serves as a key regulator in neural stem cell fate and is involved in the progression of different neurological diseases. In this research, the serum level and clinical value of RMST in Parkinson’s disease (PD) patients were detected, and the underlying mechanism was explored. <b><i>Methods:</i></b> Ninety-nine PD patients and 93 healthy individuals were collected for clinical experiments. SH-SY5Y cells were treated with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>) to establish PD cell models. qRT-PCR was used for the detection of mRNA levels. CCK-8 and flow cytometry were used to detect neuronal viability and apoptosis. The target relationship of RMST with miR-15a-5p was confirmed applying luciferase reporter assay. <b><i>Results:</i></b> RMST was present at high levels in both serum of PD patients and PD cell models. Serum RMST had a certain clinical value for the diagnosis of PD with the AUC of 0.892 at a cutoff value of 1.225. Serum RMST was positively associated with the levels of TNF-α (<i>r</i> = 0.421, <i>p</i> < 0.001) and IL-1β (<i>r</i> = 0.567, <i>p</i> < 0.001) in PD patients. Knockdown of RMST alleviated the apoptosis and inflammatory response of SH-SY5Y cells induced by MPP<sup>+</sup>. miR-150-5p was the target gene of RMST and less expressed in the clinical serum samples and PD cell models. <b><i>Conclusion:</i></b> Serum RMST serves as a promising biomarker for the diagnosis of PD. RMST downregulation may regulate the occurrence and development of PD through inhibiting neuron cell apoptosis and the release of inflammatory cytokines via targeting miR-150-5p.

Long non-coding RNA RMST serves as a diagnostic biomarker in patients with carotid artery stenosis and predicts the occurrence of cerebral ischemic event: A retrospective study

“…34 In Parkinson's disease, RMST has diagnostic role in Parkinson's disease by the evidence of ROC curve, providing that RMST may have clinical values. 35 In the current observation, the predictive roles of RMST on discrimination between healthy controls and CAS patients and the prognostic significance of RMST on the outcome of CAS were clarified. As for the screening value, perhaps RMST was a biomarker on discriminating CAS patients from healthy people.…”

Emerging Potential of Exosomal Non-coding RNA in Parkinson’s Disease: A Review

“…TUG1 down-regulation improves motor coordination in PD mice while inhibiting the production of inflammation-related proteins, according to animal research. The expression of rhabdomyosarcoma 2-associated transcript (RMST) in the serum of PD patients rose as well (AUC = 0.892) ( Chen C. L. et al, 2021 ), and it was positively correlated with the expression of inflammatory factors. miR-150-5p is the target gene of RMST.…”

Integrating nutriepigenomics in Parkinson’s disease management: New promising strategy in the omics era

“…In this study, suppression of NEAT1 activity reduced α-synuclein expression, as well as cell apoptosis activator Bax/Bcl2 ratio and mediator caspase-3 ( Liu & Lu, 2018 ), suggesting the role of NEAT1 in modulating MPTP-induced α-synuclein and programmed cell death mechanisms, possibly via miR-124/KLF4 axis ( Liu et al, 2020 ). Other than that, serum PD samples and cell models are also found to express elevated levels of rhabdomyosarcoma 2-associated transcript (RMST) lncRNA ( Chen et al, 2022 ). Increased RMST lncRNA abundance has been associated with the upregulation of pro-inflammatory cytokines TNF-α and IL-1β via its target gene miR-150–5p ( Chen et al, 2022 ).…”

“…Other than that, serum PD samples and cell models are also found to express elevated levels of rhabdomyosarcoma 2-associated transcript (RMST) lncRNA ( Chen et al, 2022 ). Increased RMST lncRNA abundance has been associated with the upregulation of pro-inflammatory cytokines TNF-α and IL-1β via its target gene miR-150–5p ( Chen et al, 2022 ). In the rats PD model, inhibiting RMST lncRNA activity suppressed the TLR/NF-κB signalling pathway and reduced dopaminergic neuronal damage ( Ma et al, 2021 ).…”