INTRODUCTION Alzheimer's disease (AD) is still the fifth leading cause of death and most common dementia worldwide. To date, there is no efficient strategy that can slow down the progression of AD owing to delayed diagnosis and limited therapies. MiR-143-3p is up-regulated in serum of AD patients, yet the exact role it plays in AD pathology is still poorly understood. The aim of this study was to investigate the effect of miR-143-3p on neuronal survival. MATERIAL AND METHODS We induced neuronal differentiation in SH-SY5Y cells using all-trans-retinoic acid (RA), and Aβ1-42 was used to establish the in vitro AD cell model. The expression of tubulin β III and neuregulin-1 (NRG1) was evaluated by immunofluorescence. TUNEL assay was performed to assess cell apoptosis. Cell viability was evaluated using the Cell Counting Kit-8 assay. The binding interaction between miR-143-3p and NRG1 was verified using the luciferase reporter assay. RESULTS Typical neuronal-like axons were observed in RA-induced SH-SY5Y cells, followed by increased tubulin β III. A dramatically increased apoptotic rate and reduced cell viability were observed in the AD cell model. Then we silenced the miR-143-3p expression, and Aβ1-42 induced cell apoptosis was alleviated after miR-143-3p inhibition, accompanied by decreased cleaved caspase-3 and cleaved caspase-9 levels. Additionally, NRG1 was confirmed to be a downstream target of miR-143-3p, increased cell viability and suppressed cell apoptosis after miR-143-3p inhibition was abolished by NRG1 knockdown. CONCLUSIONS Our findings reveal that miR-143-3p inhibition promotes neuronal survival in an in vitro cell model via targeting NRG1, and the miR-143-3p/NRG1 axis is a potential therapeutic target and promising biomarker for AD treatment.

中文翻译：

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通过靶向Neuregulin-1，miR-143-3p抑制作用可促进阿尔茨海默氏病细胞模型中的神经元存活。

引言阿尔茨海默氏病（AD）仍然是全球第五大死亡原因和最常见的痴呆症。迄今为止，由于延迟的诊断和有限的治疗方法，尚无有效的策略可以减慢AD的进展。MiR-143-3p在AD患者的血清中上调，但在AD病理中所起的确切作用仍知之甚少。这项研究的目的是调查miR-143-3p对神经元存活的影响。材料与方法我们使用全反式维甲酸（RA）诱导SH-SY5Y细胞的神经元分化，并使用Aβ1-42建立体外AD细胞模型。通过免疫荧光评估微管蛋白βIII和神经调节蛋白-1（NRG1）的表达。进行TUNEL测定以评估细胞凋亡。使用Cell Counting Kit-8测定法评估细胞活力。miR-143-3p和NRG1之间的结合相互作用已通过荧光素酶报告基因检测得以验证。结果在RA诱导的SH-SY5Y细胞中观察到典型的神经元样轴突，其次是微管蛋白βIII增加。在AD细胞模型中观察到凋亡率显着增加，细胞活力降低。然后我们沉默了miR-143-3p的表达，并抑制了miR-143-3p，减轻了Aβ1-42诱导的细胞凋亡，同时降低了caspase-3的裂解和caspase-9的裂解。此外，在NRG1敲除取消了miR-143-3p抑制作用后，证实NRG1是miR-143-3p的下游靶标，可提高细胞活力并抑制细胞凋亡。结论我们的发现表明，miR-143-3p抑制作用通过靶向NRG1促进体外细胞模型中神经元的存活，