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.

中文翻译：

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Let-7b-5p 通过靶向 HMGA2 促进帕金森病的细胞凋亡。

帕金森病 (PD) 是一种常见的多因素神经退行性疾病，其特征是黑质中多巴胺能神经元的不可逆损失。深入研究PD的发病机制具有重要意义。已经提出高流动性组 AT-hook 2 (HMGA2) 与神经元分化和认知功能障碍有关。然而，很少探讨 HMGA2 是否在 PD 中起作用。在本研究中，N-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的PD小鼠模型和N-甲基-4-苯基吡啶鎓（MPP ⁺）处理的SH-SY5Y细胞模型是已确立的。逆转录定量 PCR 显示 HMGA2 在 MPTP 处理的小鼠和 MPP ^{+的脑组织中显示出低水平}- 处理过的 SH-SY5Y 细胞。此外，HMGA2 过表达抑制 SH-SY5Y 细胞凋亡。此外，let-7b-5p与HMGA2 3'非翻译区（UTR）结合，其表达与HMGA2水平呈负相关。此外，let-7b-5p 在 PD 小鼠和 MPP+ 处理的 SH-SY5Y 细胞的脑组织中呈高水平，敲除 let-7b-5p 可抑制 SH-SY5Y 细胞凋亡。救援试验表明 HMGA2 中和了 let-7b-5p 模拟物对 SH-SY5Y 细胞凋亡的促进作用。总之，本研究表明let-7b-5p通过靶向HMGA2促进PD细胞凋亡，为研究PD的有效治疗提供了潜在的理论基础。