miR-143-3p inhibition promotes neuronal survival in an Alzheimer's disease cell model by targeting neuregulin-1.

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 A beta 1-42 was used to establish the in vitro AD cell model. The expression of tubulin beta 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 beta 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 A beta 1-42 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.