LncRNA RP11-59J16.2 Aggravates Apoptosis and Increases Tau Phosphorylation via Inhibiting MCM2 On The AD SH-SY5Y Cell Model Induced By Aβ.

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ObjectiveAlzheimer's disease (AD) is a degenerative disease of central nervous system with unclear pathogenesis, accounting for 60% - 70% of dementia cases. It is necessary to study the pathogenesis and therapeutic prospect of AD. LncRNAs have been found to play an important role in the development of AD. This study aims to explore the role of differentially expressed lncRNAs in AD patients' serum in the pathogenesis of AD.MethodsIn this study, serum microarray analysis was performed in AD patients and healthy controls to establish lncRNAs and mRNA expression profiles. The biological processes and key pathways were identified by GO analysis and KEGG pathway analysis. A protein-protein interaction network was analyzed and constructed by using String database. SH-SY5Y cells were treated with Aβ 1-42 to establish AD cell model. The expression of RP11-59J16.2 and MCM2 was detected by qRT-PCR. The mRNA binding sites and target genes of RP11-59J16.2 were predicted by bioinformatics analysis. Dual luciferase reporter gene analysis verified the targeting effect of RP11-59J16.2 on MCM2. Inhibition of RP11-59J16.2 or overexpression of MCM2, CCK-8 and flow cytometry were used to detect cell viability and apoptosis and Western Blot was used to detect the expression of p-Tau.ResultsDifferential expression of lncRNAs and mRNAs was screened by microarray data, and high expression of RP11-59J16.2 and low expression of MCM2 were detected in serum of AD patients. GO analysis and KEGG pathway analysis revealed that G1/S transition of mitotic cell cycle may be involved in the development of AD. The mRNA binding sites and target genes of RP11-59J16.2 were predicted by bioinformatics analysis. Dual luciferase reporter gene analysis, qRT-PCR and Western Blot were used to verify the targeted regulation of RP11-59J16.2 on MCM2. The expression of RP11-59J16.2 was increased and that of MCM2 was decreased in SH-SY5Y cells treated with Aβ1-42. CCK-8 assay and Annexin V FITC/PI apoptosis assay kit results showed that RP11-59J16.2 could reduce cell viability, aggravate apoptosis and increase Tau phosphorylation in AD cell model by inhibiting MCM2.ConclusionThrough gene microarray and bioinformatics analysis, high differentially expressed lncRNAs RP11-59J16.2 and low expressed mRNA MCM2 in AD patients were screened. By using bioinformatics prediction and dual luciferase reporter gene analysis, it was confirmed that RP11-59J16.2 could target MCM2 regulation. SH-SY5Y cells were treated with Aβ1-42 to construct AD cell model. Overexpression or inhibition of RP11-59J16.2 or MCM2, we found that RP11-59J16.2 could promote neuronal apoptosis and increase Tau phosphorylation by regulating MCM2 in vitro. Thus, RP11-59J16.2 might be a potential target molecule for the prediction, diagnosis and treatment of AD.