LINC00667 regulates MPP+ -induced neuronal injury in Parkinson's disease.

Abstract

ObjectiveParkinson’s disease (PD), also known as paralysis tremor, is a chronic disease of the central nervous system. It has been reported that hepatocyte nuclear factor 4 alpha (HNF4A) is upregulated in PD, but its specific function has not been well explored.MethodsWe established an in vitro PD model in SH‐SY5Y cells stimulated with 1‐methyl‐4‐phenylpyridinium (MPP+). Meanwhile, the effect of HNF4A on MPP+‐treated SH‐SY5Y cell behavior was monitored by functional assays. Mechanism assays were conducted to verify the relationship among LINC00667/miR‐34c‐5p/HNF4A. Rescue experiments validated the regulatory mechanism in PD model.ResultsThe results revealed that depletion of HNF4A suppressed cell cytotoxicity and apoptosis caused by MPP+. Knockdown of HNF4A recovered MPP+‐stimulated oxidative stress and neuroinflammation. Mechanically, HNF4A was targeted and inhibited by miR‐34c‐5p. Furthermore, we found that LINC00667 positively modulated HNF4A expression via sequestering miR‐34c‐5p in MPP+‐stimulated SH‐SY5Y cells. Interestingly, the data indicated that HNF4A could transcriptionally activate LINC00667 expression. Rescue experiments presented that miR‐34c‐5p interference or HNF4A overexpression could mitigate the effects of LINC00667 knockdown on cell viability, cytotoxicity, cell apoptosis, oxidative stress, and neuroinflammation in MPP+‐treated SH‐SY5Y cells.ConclusionOur study first proved LINC00667, miR‐34c‐5p, and HNF4A constructed a positive feedback loop in MPP+‐treated SH‐SY5Y cells, enriching our understanding of PD.