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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 <jats:italic>E. coli<\/jats:italic>-mediated neuroinflammation remains unknown. In the present study, we characterized a cytoplasm-enriched antisense lncRNA <jats:italic>DDIT4-AS1<\/jats:italic>, which showed similar concordant expression patterns with its parental mRNA <jats:italic>DDIT4<\/jats:italic> upon <jats:italic>E. coli<\/jats:italic> infection. <jats:italic>DDIT4-AS1<\/jats:italic> modulated <jats:italic>DDIT4<\/jats:italic> expression at both mRNA and protein levels. Mechanistically, <jats:italic>DDIT4-AS1<\/jats:italic> promoted the stability of <jats:italic>DDIT4<\/jats:italic> mRNA through RNA duplex formation. <jats:italic>DDIT4-AS1<\/jats:italic> knockdown and <jats:italic>DDIT4<\/jats:italic> knockout both attenuated <jats:italic>E. coli<\/jats:italic>-induced NF-\u03baB signaling as well as pro-inflammatory cytokines expression, and <jats:italic>DDIT4-AS1<\/jats:italic> regulated the inflammatory response by targeting <jats:italic>DDIT4<\/jats:italic>. In summary, our results show that <jats:italic>DDIT4-AS1<\/jats:italic> promotes <jats:italic>E. coli<\/jats:italic>-induced neuroinflammatory responses by enhancing the stability of <jats:italic>DDIT4<\/jats:italic> mRNA through RNA duplex formation, providing potential nucleic acid targets for new therapeutic interventions in the treatment of bacterial meningitis.<\/jats:p>","DOI":"10.1007\/s12035-021-02690-6","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T15:02:51Z","timestamp":1641394971000},"page":"1351-1365","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Long Non-coding Antisense RNA DDIT4-AS1 Regulates Meningitic Escherichia coli-Induced Neuroinflammation by Promoting DDIT4 mRNA Stability"],"prefix":"10.1007","volume":"59","author":[{"given":"Bo","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruicheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyang","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanchun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0191-1378","authenticated-orcid":false,"given":"Xiangru","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,5]]},"reference":[{"issue":"1","key":"2690_CR1","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/S1473-3099(09)70306-8","volume":"10","author":"KS Kim","year":"2010","unstructured":"Kim KS (2010) Acute bacterial meningitis in infants and children. 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