Abstract
BackgroundLong non-coding RNA small molecule RNA host gene 1 (SNHG1) was previously identified to be relevant with Parkinson’s disease (PD) pathogenesis. This work aims to further elucidate the regulatory networks of SNHG1 involved in PD.Methods1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP)-induced mice and 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells were respectively constructed as the in vivo and in vitro PD models. Expression levels of SNHG1 and miR-153-3p were detected by qRT-PCR. Protein expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) were measured by western blotting assay. Cell viability and apoptosis were determined by MTT and flow cytometry assays. The interactions among SNHG1, miR-153-3p and PTEN were identified by luciferase reporter assay, RNA immunoprecipitation, and/or RNA pull-down analysis.ResultsIncreased SNHG1 expression was found in midbrain of MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. Overexpression of SNHG1 lowered viability and enhanced apoptosis in MPP+-treated SH-SY5Y cells. Moreover, SNHG1 acted as a molecular sponge to inhibit the expression of miR-153-3p. Furthermore, miR-153-3p-mediated suppression of MPP+-induced cytotoxicity was abated following SNHG1 up-regulation. Additionally, PTEN was identified as a direct target of miR-153-3p, and SNHG1 could serve as a competing endogenous RNA (ceRNA) of miR-153-3p to improve the expression of PTEN. Besides, enforced expression of PTEN displayed the similar functions as SNHG1 overexpression in regulating the viability and apoptosis of MPP+-treated SH-SY5Y cells. Finally, SNHG1 was found to activate PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells by targeting miR-153-3p.ConclusionSNHG1 aggravates MPP+-induced cellular toxicity in SH-SY5Y cells by regulating PTEN/AKT/mTOR signaling via sponging miR-153-3p, indicating the potential of SNHG1 as a promising therapeutic target for PD.
Highlights
Long non-coding RNA small molecule RNA host gene 1 (SNHG1) was previously identified to be relevant with Parkinson’s disease (PD) pathogenesis
Overexpression of SNHG1 inhibited viability and induced apoptosis in MPP+‐treated SH‐SY5Y cells To investigate the function of SNHG1 in PD, MPTP and MPP+ were individually applied to induce the PD phenotype in vivo and in vitro. qRT-PCR results showed that SNHG1 expression was significantly increased in the midbrain of MPTP-induced PD mice compared with control mice (Fig. 1a)
To illustrate the potential effects of SNHG1 on the PD pathogenesis, SH-SY5Y cells were transfected with si-SNHG1 or pcDNA3.1 empty vector (pcDNA)-SNHG1 to down-regulate or up-regulate the SNHG1 expression (Fig. 1c)
Summary
Long non-coding RNA small molecule RNA host gene 1 (SNHG1) was previously identified to be relevant with Parkinson’s disease (PD) pathogenesis. This work aims to further elucidate the regulatory networks of SNHG1 involved in PD. Typical pathological characteristics of PD contain the relatively-selective loss of dopaminergic (DA) neurons in the substantia nigra pars. Zhao et al Biol Res (2020) 53:1 compacta (SNpc) of the brain, the decrease of dopamine secretion in the striatum pathway, and the formation of intracellular inclusions-Lewy body (LB) in the cytoplasm of the remaining dopamine neurons [2]. Major clinical symptoms of PD patients involve the changes of both non-motor and motor functions, such as the dyskinesia, dystonia, gait disorder and postural abnormality [3]. Though enormous efforts have been dedicated to illustrate the molecular mechanisms of PD etiology, there still lacks effective targeted drugs and therapeutic strategies for PD patients
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