2. Academic Validation
  3. Long Non-coding Antisense RNA DDIT4-AS1 Regulates Meningitic Escherichia coli-Induced Neuroinflammation by Promoting DDIT4 mRNA Stability

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

  • Mol Neurobiol. 2022 Mar;59(3):1351-1365. doi: 10.1007/s12035-021-02690-6.
Bo Yang 1 2,  Bojie Xu 1 2,  Ruicheng Yang 1 2,  Jiyang Fu 1 2,  Liang Li 1 2,  Dong Huo 1 2,  Jiaqi Chen 1 2,  Xiaopei Yang 1 2,  Chen Tan 1 2 3 4,  Huanchun Chen 1 2 3 4,  Xiangru Wang 5 6 7 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
  • 2 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, China.
  • 3 Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan, Hubei, China.
  • 4 International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, Hubei, China.
  • 5 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China. wangxr228@mail.hzau.edu.cn.
  • 6 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, China. wangxr228@mail.hzau.edu.cn.
  • 7 Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan, Hubei, China. wangxr228@mail.hzau.edu.cn.
  • 8 International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, Hubei, China. wangxr228@mail.hzau.edu.cn.
PMID: 34985734 DOI: 10.1007/s12035-021-02690-6
Abstract

Our previous studies have shown that meningitic Escherichia coli can colonize the brain and cause neuroinflammation. Controlling the balance of inflammatory responses in the host central nervous system is particularly vital. Emerging evidence has shown the important regulatory roles of long non-coding RNAs (lncRNAs) in a wide range of biological and pathological processes. However, whether lncRNAs participate in the regulation of meningitic E. coli-mediated neuroinflammation remains unknown. In the present study, we characterized a cytoplasm-enriched antisense lncRNA DDIT4-AS1, which showed similar concordant expression patterns with its parental mRNA DDIT4 upon E. coli Infection. DDIT4-AS1 modulated DDIT4 expression at both mRNA and protein levels. Mechanistically, DDIT4-AS1 promoted the stability of DDIT4 mRNA through RNA duplex formation. DDIT4-AS1 knockdown and DDIT4 knockout both attenuated E. coli-induced NF-κB signaling as well as pro-inflammatory cytokines expression, and DDIT4-AS1 regulated the inflammatory response by targeting DDIT4. In summary, our results show that DDIT4-AS1 promotes E. coli-induced neuroinflammatory responses by enhancing the stability of DDIT4 mRNA through RNA duplex formation, providing potential nucleic acid targets for new therapeutic interventions in the treatment of Bacterial meningitis.

Keywords

Antisense lncRNA; DDIT4; DDIT4-AS1; Escherichia coli; Neuroinflammation.

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