Let-7b-5p promotes cell apoptosis in Parkinson's disease by targeting HMGA2

Parkinson's disease (PD), a common multifactorial neurodegenerative disease, is characterized by irreversible loss of dopaminergic neurons in the substantia nigra. In-depth study of the pathogenesis of PD is of great importance. High-mobility group AT-hook 2 (HMGA2) has been proposed to be implicated with neuronal differentiation and impairment of cognitive function. However, whether HMGA2 plays a role in PD is rarely explored. In the present study, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated PD mice models and N-methyl-4- phenylpyridinium (MPP+)-treated SH-SY5Y cell models were established. Reverse transcription-quantitative PCR showed that HMGA2 displayed low levels in brain tissues of MPTP-treated mice and MPP+-treated SH-SY5Y cells. Moreover, HMGA2 overexpression suppressed SH-SY5Y cell apoptosis. Additionally, let-7b-5p bound with HMGA2 3 ' untranslated region (UTR), and its expression was negatively correlated with HMGA2 level. Moreover, let-7b-5p presented high levels in brain tissues of PD mice and MPP+-treated SH-SY5Y cells, and knockdown of let-7b-5p inhibited SH-SY5Y cell apoptosis. Rescue assays illustrated that HMGA2 neutralized the promotive effects of let-7b-5p mimics on SH-SY5Y cell apoptosis. In conclusion, the present study demonstrated that let-7b-5p contributes to cell apoptosis in PD by targeting HMGA2, which offers a potential theoretical basis for the study of effective therapy in PD.

Automated summary

This study discovered that let-7b-5p promotes cell apoptosis in PD by targeting HMGA2, providing a potential theoretical basis for effective therapy in PD.