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This study was designed to investigate the functional mechanisms of long noncoding RNA growth arrest\u2010specific transcript 5 (lncRNA GAS5) on lipopolysaccharide (LPS)\u2010induced human bronchial epithelial cell (HBEC) pyroptosis. LPS was used to induce pyroptosis in HBECs, followed by the detection of the expression of GAS5, forkhead box O3 (FOXO3), and nuclear factor E2\u2010related factor 2\/heme oxygenase 1 (Nrf2\/HO\u20101) signaling pathway\u2010related factors. Cell viability was evaluated using CCK\u20108 assay, lactate dehydrogenase (LDH) release was assessed by LDH assay kit and caspase\u20101 activity by flow cytometry. Furthermore, expression of NOD\u2010like receptor family pyrin domain containing 3 and pyroptosis\u2010related proteins was evaluated using Western blot analysis, while enzyme\u2010linked immunosorbent assay was used to determine the levels of inflammatory factors. The interaction between GAS5 and FOXO3 was confirmed using bioinformatic prediction, <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> immunoprecipitation assay, RNA pull\u2010down, and dual\u2010luciferase reporter gene assay. Treatment of HBECs with LPS upregulated the expression of GAS5 and FOXO3, resulting in the inactivation of the Nrf2\/HO\u20101 signaling pathway. On the other hand, inhibition of both GAS5 and FOXO3 promoted cell viability, reduced LDH release, pyroptosis, and inflammatory response in LPS\u2010induced HBECs. Furthermore, FOXO3 could interact with GAS5, while FOXO3 overexpression reversed the inhibitory effect of GAS5 knockdown on cell pyroptosis. Thus, mechanistically, inhibition of FOXO3 activates the Nrf2\/HO\u20101 pathway to suppress LPS\u2010induced pyroptosis in HBECs. This study revealed that GAS5 knockdown attenuates FOXO3 expression thereby activating the Nrf2\/HO\u20101 pathway to inhibit LPS\u2010induced pyroptosis in HBECs. These findings may contribute to identifying novel targets that inhibit pyroptosis in HBECs.<\/jats:p>","DOI":"10.1002\/kjm2.12452","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T14:57:07Z","timestamp":1631804227000},"page":"87-96","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Knockdown of long noncoding RNA growth arrest\u2010specific transcript 5 regulates forkhead box O3 to inhibit lipopolysaccharide\u2010induced human bronchial epithelial cell pyroptosis"],"prefix":"10.1002","volume":"38","author":[{"given":"Ling\u2010Xia","family":"Lv","sequence":"first","affiliation":[{"name":"Respiratory and Critical Care Medicine Wuhan Asia General Hospital  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Wen","sequence":"additional","affiliation":[{"name":"Respiratory and Critical Care Medicine Wuhan Asia General Hospital  Wuhan 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