Inhibition of LncRNA-NEAT1 alleviates intestinal epithelial cells (IECs) dysfunction in ulcerative colitis by maintaining the homeostasis of the glucose metabolism through the miR-410-3p-LDHA axis.

Dysfunction of intestinal epithelial cells (IECs) leads to intestinal epithelial barrier damage and critically involves in the pathogenesis and development of ulcerative colitis (UC). Accumulating studies revealed essential functions of non-coding RNAs in UC. LncRNA NEAT1 (long non-coding RNA nuclear paraspeckle assembly transcript 1) is frequently dysregulated in diverse human diseases. Currently, the precise roles of NEAT1 in the dysfunction of IECs during UC remain unclear. We report NEAT1 was significantly upregulated in IECs from UC patients. In addition, microRNA-410-3p was remarkedly suppressed in IECs from UC patients. Silencing NEAT1 effectively ameliorates the LPS-induced IECs dysfunction. Bioinformatical analysis, RNA pull-down and luciferase assays illustrated that NEAT1 sponged miR-410-3p to downregulate its expression in IECs. Interestingly, the glucose metabolism was obviously elevated in IECs from UC compared with normal colon tissues. Furthermore, NEAT1 promoted and miR-410-3p suppressed glucose metabolism of IECs. We identified lactate dehydrogenase A (LDHA), a glucose metabolism key enzyme, was a direct target of miR-410-3p in IECs. Rescue experiments verified that restoration of miR-410-3p in NEAT1-overexpressing IECs successfully overcame the NEAT1-promoted cell death under LPS treatment by targeting LDHA. In summary, these results unveiled new roles and molecular mechanisms for the NEAT1-mediated IECs dysfunction during the ulcerative colitis.