LncRNA AL133415.1 promotes neuronal apoptosis and its association with Alzheimer's disease through the regulation of miR-125b/vimentin axis

Abstract

Abstract Background Accumulating studies have identified that long noncoding RNA (lncRNA) are novel regulators in Alzheimer’s disease (AD). The goal of this study is to examine the impact of LncRNAAL133415.1 on cell viability, neuronal apoptosis, and oxidative stress and to further investigate the molecular mechanisms in AD. Methods In our study, we transfected control overexpression, lncRNA AL133415.1 overexpression, control siRNA, and lncRNA AL133415.1 siRNA into an SH-SY5Y-based AD cell model that was established using Aβ42 insult. We then measured cell viability and apoptosis using a CCK-8 assay and apoptosis marker expressions. Oxidative stress was assessed using a reactive oxygen species assay Kit and RT-qPCR was used to make observations. Total proteins were extracted and quantified using Western blot assays. We also determined the expression of Vimentin in each group. Results Transcriptome analysis revealed that vimentin (VIM) is a cis-target gene regulated by lncRNA AL133415.1. TargetScan database showed that VIM is a promising candidate target gene for miR-138-5p. In AD cell model, overexpression of lncRNA AL133415.1 inhibited cell viability and promoted cell apoptosis, while silencing lncRNA AL133415.1 had the opposite effect. Similarly, overexpression of lncRNA AL133415.1 inhibited Vimentin expression, while silencing lncRNA AL133415.1 promoted Vimentin expression. Overexpression of miR-138-5p also inhibited Vimentin expression, while inhibition of miR-138-5p expression promoted Vimentin expression. The levels of ROS were reduced in the lncRNA AL133415.1 silence group and increased in the lncRNA AL133415.1 overexpression group. Conversely, SOD levels were increased in the lncRNA AL133415.1 silence group and decreased in the lncRNA AL133415.1 overexpression group. Conclusion LncRNA AL133415.1 may interact with miR-138-5p to increase neuron cell death and reduce the expression of Vimentin in AD.