Profiling of Long Non-coding RNAs and mRNAs by RNA-Sequencing in the Hippocampi of Adult Mice Following Propofol Sedation

Abstract

Propofol is a frequently used intravenous anesthetic agent. The impairment caused by propofol on the neural system, especially the hippocampus, has been widely reported. However, the molecular mechanism underlying the effects of propofol on learning and memory functions in the hippocampus is still unclear. In the present study we performed lncRNA and mRNA analysis in the hippocampi of adult mice, after propofol sedation, through RNA-Sequencing (RNA-Seq). A total of 146 differentially expressed lncRNAs and 1103 mRNAs were identified. Bioinformatics analysis, including gene ontology (GO) analysis, pathway analysis and network analysis, were done for the identified dysregulated genes. Pathway analysis indicated that the FoxO signaling pathway played an important role in the effects of propofol on the hippocampus. Finally, four lncRNAs and three proteins were selected from the FoxO-related network for further validation. The up-regulation of lncE230001N04Rik and the down-regulation of lncRP23-430H21.1 and lncB230206L02Rik showed the same fold change tendencies but changes in Gm26532 were not statistically significant in the RNA-Seq results, following propofol sedation. The FoxO pathway-related proteins, PI3K and AKT, are up-regulated in propofol-exposed group. FoxO3a is down-regulated at both mRNA and protein levels. Our study reveals that propofol sedation can influence the expression of lncRNAs and mRNAs in the hippocampus, and bioinformatics analysis have identified key biological processes and pathways associated with propofol sedation. Cumulatively, our results provide a framework for further study on the role of lncRNAs in propofol-induced or -related neurotoxicity, particularly with regards to hippocampus-related dysfunction.

Recent progress on the role of non-coding RNA in postoperative cognitive dysfunction

“…As a known regulator of miR-21, signal transducer and activator of transcription 3 plays a key role in propofol-induced neurotoxicity by mediating the miR-21/sprout 2/Akt pathway ( Twaroski et al, 2014 ). Meanwhile, a recent RNA-sequencing analysis revealed that propofol-based sedatives may up-regulate FoxO pathway-related proteins (PI3K and Akt) and down-regulate FoxO3a at both the RNA and protein levels via differently expressed lncRNAs (lncE230001N04Rik, lncRP23-430H21.1, and lncB230206L02Rik) ( Fan et al, 2018 ). In in vitro PC-12 cells and rat brain tissues, circ-001372 suppressed propofol-induced neurotoxicity and neuroinflammation through the PI3K/Akt signaling pathway ( Wang et al, 2021a ).…”

Propofol Suppresses Proinflammatory Cytokine Production by Increasing ABCA1 Expression via Mediation by the Long Noncoding RNA LOC286367

“…A recent experiment using the hippocampi of adult mice has revealed a mechanism of propofol in the regulation of lncRNAs. The study showed that propofol sedation can impact the expression of lncRNAs and mRNA in the hippocampus via the FoxO pathway-related proteins phosphatidylinositol 3-kinase and protein kinase B [37]. Intriguingly, the results of microarray analysis, qPCR, and Western blot assays performed in this study showed that propofol also exhibited an anti-inflammatory effect on THP-1 macrophages via inhibiting lncRNA-LOC286367 expression.…”

Propofol suppresses proliferation, migration, invasion, and tumor growth of liver cancer cells via suppressing cancer susceptibility candidate 9/phosphatase and tensin homolog/AKT serine/threonine kinase/mechanistic target of rapamycin kinase axis

“…Transcriptome RNA sequencing was carried out as described previously. 22 SNU-449 and HuH-6 cells (5 × 10 5 ) were seeded in 6-well plates and treated with 25 μg/mL propofol or equal volume of DMSO for 48 h, then cells were collected for total RNAs extraction using RNeasy Mini kit (Qiagen). NEB Next Ultra II Directional RNA Library Prep kit (New England BioLabs) was used to generate RNA-seq libraries.…”