Long noncoding RNA BACE1-antisense transcript plays a critical role in Parkinson’s disease via microRNA-214-3p/Cell death-inducing p53-target protein 1 axis

ABSTRACT

This study aimed to analyze the function and latent mechanism of long noncoding RNA BACE1-antisense transcript (lncRNA BACE1-AS) in MPP ⁺-induced SH-SY5Y cells. SH-SY5Y cells were cultivated in 1 mM MPP ⁺ for 24 h to establish Parkinson’s disease (PD) model in vitro. TargetScan and luciferase reporter assay were conducted to predict and verify the interaction between microRNA (miR)-214-3p and CDIP1 (Cell death-inducing p53-target protein 1). Cell viability, lactate dehydrogenase (LDH) release, and cell apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT), LDH, and flow cytometer. The secretion of inflammatory factors and representative biomarkers of oxidative stress, including reactive oxygen species (ROS) and superoxide dismutase (SOD) were assessed using enzyme-linked immunosorbent assay (ELISA) and specific assay kits. Results suggested that lncRNA BACE1-AS was over-expressed and miR-214-3p was under-expressed in MPP ⁺-stimulated SH-SY5Y cells. Further analyses revealed that MPP ⁺ inhibited cell viability; enhanced cell apoptosis, Cleaved Caspase-3 expression and Cleaved Caspase-3/GAPDH ratio; induced oxidative stress and inflammation in SH-SY5Y cells were inhibited by lncRNA BACE1-AS-siRNA transfection; and all these inhibitions were reversed by miR-214-3p inhibitor. In addition, we found that CDIP1 was directly targeted by miR-214-3p and up-regulated in MPP ⁺-stimulated SH-SY5Y cells. Further functional assays suggested that CDIP1-plasmid reversed the effects of miR-214-3p mimic on MPP ⁺-stimulated SH-SY5Y cells. In conclusion, lncRNA BACE1-AS regulates SH-SY5Y cell proliferation, apoptosis, inflammatory response, and oxidative stress through direct regulation of miR-214-3p/CDIP1 signaling axis, and could be a potential candidate associated with the diagnosis and treatment of PD.

Graphical abstract