Knockdown of long non‑coding RNA NEAT1 relieves inflammation of ulcerative colitis by regulating the miR‑603/FGF9 pathway

Abstract

Ulcerative colitis (UC) is a significant threat to human life. Hence, there is an urgent requirement to understand the mechanism of UC progression and to develop novel therapeutic interventions for the treatment of UC. The present study aimed to evaluate the potential significance of long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) in the progression of UC. NEAT1 expression was detected in colonic mucosa samples from patients with UC and healthy individuals. Fetal human cells (FHCs) were treated with different concentrations of lipopolysaccharides (LPS) to induce UC-caused inflammatory injury, and the effects of NEAT1 knockdown were investigated on cytokines production, cell apoptosis and viability. Furthermore, the correlation and regulation between NEAT1 and microRNA (miRNA/miR)-603 and the fibroblast growth factor 9 (FGF9) pathway were investigated. The results demonstrated that NEAT1 expression was upregulated in the colonic mucosa tissues of patients with UC. In addition, significant cell injury was observed in FHCs treated with different concentrations of LPS, with decreased cell viability, and increased apoptosis and inflammatory cytokines production. Conversely, NEAT1 knockdown significantly reduced LPS-induced cell injury in FHCs, which was achieved through negative regulation of miR-603 expression. Furthermore, FGF9 was negatively regulated by miR-603, and thus, FGF9 was identified as a potential target of miR-603. Notably, FGF9 knockdown reversed the suppressing effects of miR-603 on LPS-induced injury in FHCs. Taken together, the results of the present study suggest that NEAT1 contributes to the development of UC by regulating the miR-603/FGF9 pathway.

Identification of Critical Modules and Biomarkers of Ulcerative Colitis by Using WGCNA

“…In addition, the lncRNAs XIST and NEAT1 have been linked to the process of inflammation in UC. [77][78][79] The predicted lncRNA XIST, together with two essential miRNAs, may all play important roles in UC progression. Nonetheless, the ceRNA mechanisms underlying UC remained mostly unclear, demanding more study.…”