AbstractBackgroundLong noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been reported to play regulatory roles in ulcerative colitis (UC). In this study, we aimed to determine the specific roles and action mechanism of the nuclear paraspeckle assembly transcript 1 (NEAT1) in UC.MethodsReverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) was used to determine the lncRNANEAT1andmiR‐493‐5pexpression levels in patients with UC and healthy volunteers. We determine the forecast linkage points ofNEAT1andmiR‐493‐5pusing Starbase and those ofmiR‐493‐5pandRab27Ausing TargetScan, and further verified them using a double luciferase gene reporter kit. RT‐qPCR and Western blot analysis were used to determine the lncRNANEAT1,miR‐493‐5p, andRab27Aexpression levels in lipopolysaccharide (LPS)‐induced Caco‐2 cells. Flow cytometry and cell counting kit‐8 were used to assess Caco‐2 cell viability. Tumor necrosis factor‐α, interleukin (IL)‐6, IL‐8, and IL‐1β levels were determined via an enzyme‐linked immunosorbent assay.ResultsExpression levels ofNEAT1were upregulated and those of miR‐493‐5p were downregualted in 10 ng/mL LPS‐treated Caco‐2 cells and patients with UC. Dual‐luciferase gene reporter assay revealed thatmiR‐493‐5pis linked toNEAT1, andRab27Ais a downstream target ofmiR‐493‐5p. Overexpression of miR‐493‐5pinhibited the apoptosis and inflammation in LPS‐treated Caco‐2 cells. Moreover, downregulation of lncRNANEAT1expression also inhibited the apoptosis and inflammation in LPS‐treated Caco‐2 cells, which was reversed by Rab27A plasmid cotransfection.ConclusionOur results revealed thatNEAT1participates in UC progression by inhibitingmiR‐493‐5pexpression.