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Long Non-coding Antisense RNA DDIT4-AS1 Regulates Meningitic Escherichia coli-Induced Neuroinflammation by Promoting

Bo Yang1,2, Bojie Xu1,2, Ruicheng Yang1,2

  • 1State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.

Molecular Neurobiology
|January 5, 2022
PubMed

Insights

Long non-coding RNA DDIT4-AS1 promotes bacterial meningitis by stabilizing DDIT4 mRNA, enhancing neuroinflammation. This finding offers potential nucleic acid targets for treating meningitis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Immunology

Background:

  • Meningitic Escherichia coli colonizes the brain, causing neuroinflammation.
  • Long non-coding RNAs (lncRNAs) regulate biological and pathological processes.
  • The role of lncRNAs in E. coli-induced neuroinflammation is unknown.

Purpose of the Study:

  • To investigate the role of lncRNAs in meningitic E. coli-mediated neuroinflammation.
  • To characterize the function and mechanism of lncRNA DDIT4-AS1 in E. coli infection.

Main Methods:

  • Characterization of cytoplasm-enriched antisense lncRNA DDIT4-AS1.
  • Analysis of DDIT4-AS1 expression and its correlation with DDIT4 mRNA and protein levels.
  • Investigation of DDIT4-AS1's mechanism involving RNA duplex formation and mRNA stability.
  • Assessment of E. coli-induced NF-κB signaling and pro-inflammatory cytokine expression following DDIT4-AS1 knockdown or DDIT4 knockout.

Main Results:

  • DDIT4-AS1 expression is concordant with DDIT4 upon E. coli infection.
  • DDIT4-AS1 enhances DDIT4 mRNA and protein stability via RNA duplex formation.
  • DDIT4-AS1 knockdown and DDIT4 knockout attenuate E. coli-induced NF-κB signaling and pro-inflammatory cytokine production.
  • DDIT4-AS1 regulates the inflammatory response by targeting DDIT4.

Conclusions:

  • DDIT4-AS1 promotes E. coli-induced neuroinflammation by stabilizing DDIT4 mRNA.
  • DDIT4-AS1 serves as a regulator of neuroinflammatory responses in bacterial meningitis.
  • DDIT4-AS1 represents a potential nucleic acid target for therapeutic interventions against bacterial meningitis.
Keywords:
Antisense lncRNADDIT4DDIT4-AS1Escherichia coliNeuroinflammation

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