miR-29c-3p regulates TET2 expression and inhibits autophagy process in Parkinson's disease models,Genes to Cells

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miR-29c-3p regulates TET2 expression and inhibits autophagy process in Parkinson's disease models
Genes to Cells ( IF 1.3 ) Pub Date : 2021-06-04 , DOI: 10.1111/gtc.12877
Ruili Wang ₁ , Jie Yao ₁ , Fuhua Gong ₁ , Songsheng Chen ₁ , Ya He ₁ , Chunting Hu ₁ , Chen Li ₁

Affiliation

Autophagy in dopamine (DA) neurons is concerned to be associated with Parkinson's disease (PD), but the detailed mechanism remains unknown. Herein, we aimed to investigate the function of microRNA (miR)-29c-3p in autophagy in PD models. Intraperitoneal injection of MPTP (20 mg/kg) was given to C57BL/6 mice to establish PD mouse model. SH-SY5Y cells were treated with MPP⁺ (1 mmol/L) to establish in vitro PD model. The results indicated that in the substantia nigra pars compacta (SNpc) DA neurons of PD mice, autophagy was activated accompanied by down-regulated miR-29c-3p and up-regulated ten-eleven translocation 2 (TET2) expression. Up-regulation of miR-29c-3p inhibited TET2 expression and SNpc (including DA neurons) autophagy in PD mice. In vitro PD model confirmed that MPP⁺ treatment markedly down-regulated miR-29c-3p expression and up-regulated TET2 expression in SH-SY5Y cells in a dose/time-dependent manner. Moreover, miR-29c-3p up-regulation also inhibited autophagy and TET2 expression in vitro. Additionally, TET2 was proved to be targeted and down-regulated by miR-29c-3p. TET2 knockdown inhibited MPP⁺-induced autophagy, whereas TET2 over-expression reversed the effects of miR-29c-3p over-expression on SH-SY5Y cell autophagy. Overall, miR-29c-3p over-expression inhibits autophagy in PD models, which may be mediated by TET2. Our finding may provide new insights for regulating autophagy to improve PD progression.

中文翻译：

miR-29c-3p 调节 TET2 表达并抑制帕金森病模型中的自噬过程

多巴胺 (DA) 神经元中的自噬被认为与帕金森病 (PD) 相关，但详细机制尚不清楚。在此，我们旨在研究 microRNA (miR)-29c-3p 在 PD 模型中自噬中的功能。C57BL/6小鼠腹腔注射MPTP(20 mg/kg)建立PD小鼠模型。用MPP ⁺ (1 mmol/L)处理SH-SY5Y细胞建立体外PD模型。结果表明，在 PD 小鼠的黑质致密部 (SNpc) DA 神经元中，自噬被激活，伴随着 miR-29c-3p 的下调和 10-11 易位 2 (TET2) 的表达上调。miR-29c-3p 的上调抑制了 PD 小鼠的 TET2 表达和 SNpc（包括 DA 神经元）自噬。体外 PD 模型证实 MPP ⁺治疗以剂量/时间依赖性方式显着下调 SH-SY5Y 细胞中的 miR-29c-3p 表达和上调 TET2 表达。此外，miR-29c-3p 上调还在体外抑制自噬和 TET2 表达。此外，证明 TET2 被 miR-29c-3p 靶向和下调。TET2 敲低抑制 MPP ⁺诱导的自噬，而 TET2 过表达逆转了 miR-29c-3p 过表达对 SH-SY5Y 细胞自噬的影响。总的来说，miR-29c-3p 过表达抑制了 PD 模型中的自噬，这可能是由 TET2 介导的。我们的发现可能为调节自噬以改善 PD 进展提供新的见解。

更新日期：2021-06-04

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