LncRNA NORAD sponging to miR-26b-5p represses the progression of Alzheimer’s disease in vitro by upregulating MME expression

Abstract

Alzheimer’s disease (AD) is a progressive neurological condition that causes brain shrinkage and cell death. This study aimed to identify the role of the NORAD/miR-26b-5p axis in AD. StarBase was used to examine the binding sequences of miR-26b-5p to LncRNA NORAD or its target genes, which were verified by a double luciferase reporter assay. PC12 cells were processed with Aβ1-42 to construct an AD model in vitro, and LncRNA NORAD and miR-26b-5p levels in PC12 cells were identified by RT-qPCR. Cell viability and apoptosis were measured using the MTT assay and flow cytometry, respectively. LDH release and oxidative stress-related indicators (MDA, SOD, and CAT) were detected using the corresponding kits, and the levels of Bcl-2 and Bax were assessed by western blotting and RT-qPCR. Aβ1-42 distinctly decreased LncRNA NORAD and membrane metalloendopeptidase (MME) levels in PC12 cells, while miR-26b-5p was generally increased. The LncRNA NORAD can adsorb miR-26b-5p, and the target gene of miR-26b-5p is neprilysin (MME). In the Aβ1-42 induced AD model, PC12 cell activity decreased, LDH release and apoptosis increased, oxidative stress level increased, Bax expression increased, and Bcl-2 expression decreased. LncRNA NORAD plays a protective role in AD cell models by abrogating miR-26b-5p levels. Inhibition of MME expression eliminated the protective effects of the miR-26b-5p inhibitor in AD cell models. LncRNA NORAD inhibits AD progression in vitro by modulating the miR-26b-5p–MME signaling axis. The LncRNA NORAD/miR-26b-5p is expected to be a prospective therapeutic candidate for AD.