In-depth analyses of lncRNA and circRNA expression in the hippocampus of LPS-induced AD mice by Byu d Mar 25

Abstract

Byu d Mar 25 (BM25) has been verified to have neuroprotective effects in Alzheimer’s disease (AD) mice. However, the molecular mechanism remains unclear. We aimed to investigate the expression profiling of lncRNAs and circRNAs by microarray analysis. Six hippocampus from LPS-mediated AD mice model treated with (normal saline (NS) (n = 3) and AD mice model treated with BM25 (n = 3) were selected. Microarray analysis was performed to detect the expression profiles of lncRNAs and circRNAs in hippocampus. Differentially expressed (DE) lncRNAs, mRNAs and circRNAs were identified through scatter plot and volcano plot filtering with a threshold of fold-change ≥2 and P ≤ 0.05. Co-expression network is analyzed by Circos software. Cis- and Trans- regulation were analyzed using RIsearch-2.0 and FEELNC softwares. LncRNA-transcription factors (TFs) and LncRNA-Target-TFs network were analyzed by Clusterprofiler software. The prediction of miRNAs bind to circRNAs were performed with miRNAbase. A total of 113 DElncRNAs, 117 DEmRNAs, and 4 DEcircRNAs were detected. The pathway analysis showed the mRNAs that correlated with lncRNAs were involved in apoptosis, inflammatory mediator regulation of TRP channels, NF-kappa B and PI3K-Akt signaling pathway. The lncRNA-TFs network analysis suggested the lncRNAs were mostly regulated by Ncoa1, Phf5a, Klf6, Lmx1b, and Pax3. Additionally, lncRNA-target-TFs network analysis indicated the GATA6, Junb, Smad1, Twist1, and Mafb mostly regulate the same lncRNAs: XR_001783430.1 and NR_051982.1. Furthermore, 480 miRNAs were predicted binding to 4 identified circRNAs. The BM25 may affect AD by regulating the expression of lncRNAs and circRNAs, which could regulate the expressions of mRNAs or miRNAs by LncRNA-Target-TFs network.