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

Parkinson'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.

We 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.

The 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.

Our 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.