Comprehensive analysis of mRNAs, lncRNAs and circRNAs in the early phase of microglial activation

Exp Ther Med. 2021 Dec;22(6):1460. doi: 10.3892/etm.2021.10895. Epub 2021 Oct 20.

Abstract

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis that may seriously affect the prognosis and quality of life of patients with sepsis. Microglial activation is vital to the neuroinflammation and the pathology of SAE. In the present study, in vitro cultured BV-2 microglial cells stimulated with lipopolysaccharide (LPS) were employed as a model of microglia activation. The altered profiles of long noncoding (lnc)RNAs, circular (circ)RNAs and mRNAs in BV-2 cells after 4 h of LPS exposure were arrayed by using the Agilent competing endogenous (ce)RNA Microarray Chip. Using fold change >2 and P<0.05 as the cutoff criteria, 1,135 mRNAs and 2,488 lncRNAs were determined to be upregulated and 630 mRNAs and 744 lncRNAs to be downregulated. The number of differentially expressed circRNAs was lower, with 140 upregulated and 123 downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of DE mRNAs suggested that inflammatory responses, as well as lipid metabolism, were involved in microglial activation. Furthermore, analyses of ceRNA networks of the lncRNA-miRNA-mRNA or circRNA-miRNA-mRNA interrelations were performed. The present study revealed a multitude of novel candidate mRNAs, lncRNAs and circRNAs involved in microglial activation, which may improve the current knowledge on neuroinflammation and provide potential therapeutic targets for SAE.

Keywords: circular RNA; long non-coding RNA; microglia activation; neuroinflammation; sepsis-associated encephalopathy.

Grants and funding

Funding: This work was supported by the Natural Science Foundation of Anhui Province (grant no. 1808085MH308) and the School Research Fund Project of Anhui Medical University (grant no. 2019xkj178).