Analysis of differentially expressed long non-coding RNAs in LPS-induced human HMC3 microglial cells

BMC Genomics. 2022 Dec 27;23(1):853. doi: 10.1186/s12864-022-09083-6.

Abstract

Background: Long non-coding RNAs (lncRNAs) are emerging as key modulators of inflammatory gene expression, but their roles in neuroinflammation are poorly understood. Here, we identified the inflammation-related lncRNAs and correlated mRNAs of the lipopolysaccharide (LPS)-treated human microglial cell line HMC3. We explored their potential roles and interactions using bioinformatics tools such as gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG), and weighted gene co-expression network analysis (WGCNA).

Results: We identified 5 differentially expressed (DE) lncRNAs, 4 of which (AC083837.1, IRF1-AS1, LINC02605, and MIR3142HG) are novel for microglia. The DElncRNAs with their correlated DEmRNAs (99 total) fell into two network modules that both were enriched with inflammation-related RNAs. However, treatment with the anti-inflammatory agent JQ1, an inhibitor of the bromodomain and extra-terminal (BET) protein BRD4, neutralized the LPS effect in only one module, showing little or even enhancing effect on the other.

Conclusions: These results provide insight into, and a resource for studying, the regulation of microglia-mediated neuroinflammation and its potential therapy by small-molecule BET inhibitors.

Keywords: BET inhibitor; Differentially expressed long non-coding RNAs (DElncRNAs); Differentially expressed mRNAs (DEmRNAs); Human microglia; JQ1; Long non-coding RNA (LncRNA); Neuroinflammation; RNA sequencing (RNA-seq).

MeSH terms

  • Cell Cycle Proteins / genetics
  • Gene Regulatory Networks
  • Humans
  • Inflammation / genetics
  • Lipopolysaccharides* / pharmacology
  • Microglia / metabolism
  • Neuroinflammatory Diseases
  • Nuclear Proteins / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Transcription Factors / genetics

Substances

  • Lipopolysaccharides
  • RNA, Long Noncoding
  • Nuclear Proteins
  • Transcription Factors
  • BRD4 protein, human
  • Cell Cycle Proteins