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

Abstract

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.

IgG from Adult Atopic Dermatitis (AD) Patients Induces Thymic IL-22 Production and CLA Expression on CD4+ T Cells: Possible Epigenetic Implications Mediated by miRNA

“…The modulation of these miRNAs is consistent with previous studies and is involved in several cellular processes, including cell proliferation, differentiation, immune response, and apoptosis [ 51 , 52 , 53 , 54 , 55 , 56 ]. For instance, a high expression of miR-181b-5p levels has been detected in the thymus [ 27 ].…”

miRNAs as a Potential Biomarker in the COVID-19 Infection and Complications Course, Severity, and Outcome

“…This proinflammatory miRNA overexpression accelerates inflammation in the CNS trough targeting various anti-inflammatory regulators, increasing the permeability of the blood–brain barrier and T lymphocyte activation, leading to beta-amyloid plaque formation [ 101 , 102 , 103 , 104 ]. Let-7b is another miRNA that is overexpressed in COVID-19 patients and in neurodegenerative disorders, such as AD and PD, and a possible common mechanism is apoptosis promotion [ 105 , 106 ]. This miRNA has been downregulated in anti-NMDA encephalitis and proposed as a biomarker for this condition [ 107 ].…”

MicroRNAs in the epigenetic regulation of disease progression in Parkinson’s disease

“…Let-7b-5p knockdown prevented SH-SY5Y cell death. The study found that let-7b-5p contributes to cell apoptosis in PD via targeting HMGA2, thus providing a therapeutic target for PD (Huang et al, 2021). In one of the studies, miR-29b2/c was found to be involved in aging and disease progression in PD.…”