LncRNA UCA1 Accelerates the Progression of Ulcerative Colitis via Mediating the miR-331-3p/BRD4 Axis

Abstract

Background Ulcerative colitis (UC) has become one of the fastest-growing severe diseases worldwide with high morbidity. This research aimed to explore the function of lncRNA UCA1 in UC progression. Methods RT-qPCR analysis was used to examine the expression of UCA1 level in colonic mucosa tissues of UC patients. Then, fetal human cells (FHCs) were stimulated by LPS to induce inflammatory injury. CCK-8, flow cytometry and ELISA were adopted to determine the influence of UCA1 depletion on cell viability, apoptosis and pro-inflammatory factors levels in LPS-induced FHCs. The interaction between UCA1 and miR-331-3p or BRD4 was confirmed by luciferase reporter assay. The expressions of key factors involved in NF-κB pathway were assessed by Western blotting. Results LncRNA UCA1 level was elevated in colonic mucosa tissues of UC patients. LPS stimulation restrained cell viability and promoted the apoptosis and inflammatory factors levels, thus inducing FHCs inflammatory injury, while these effects were partially abolished by UCA1 knockdown. Moreover, it was found that UCA1 silence improved LPS-triggered cell injury via miR-331-3p. In addition, BRD4 was directly targeted by miR-331-3p, and BRD4 deficiency neutralized the effects of miR-331-3p repression on LPS-triggered injury in LPS-treated FHCs. Conclusion Our data determined that UCA1 knockdown attenuated UC development via targeting the miR-331-3p/BRD4/NF-κB pathway.

Expression profile of serum LncRNAs MALAT-1 and CCAT-1 and their correlation with Mayo severity score in ulcerative colitis patients can diagnose and predict the prognosis of the disease

“…Enduring inflammation of the colon epithelia has been linked to the initiation of colorectal cancer [ 21 ]. Recent studies revealed a different expression pattern of ncRNAs between healthy, inflamed, adenocarcinoma and cancerous tissue of colonic tissues suggesting that ncRNAs may be promising prognostic and diagnostic markers and therapeutic targets [ 21 , 22 ].…”

Mechanism of lncRNA-H19 in Intestinal Injury of Mice with Ulcerative Colitis

“…In this study, H19 was demonstrated to locate in the cytoplasm through the lncATLAS website prediction and nuclear/cytosol fractionation assay, suggesting that H19 could act as a ceRNA to play a role in UC. Prior research unveiled that miR-331-3p depletion aggravates inflammation and apoptosis in UC [17]. The binding relationship of H19 and miR-331-3p was testified via RNA pull-down and dual-luciferase assays.…”

“…Subsequently, target miRNAs of H19 were predicted with the aid of the Starbase database. Prior studies have demonstrated that miR-331-3p is involved in inflammatory responses in multiple diseases and plays a crucial role in UC development [15,17]. Hence, we se-Fig.…”

“…miR-331-3p was identified as a gene that participates in the termination of inflammation in multiple diseases [15,16]. Particularly, miR-331-3p was noted to be decreased in UC tissues and fight against inflammation and apoptosis of colorectal cells [17]. Tumor necrosis factor receptor-associated factor 4 (TRAF4) is well-known for its function as an E3 ubiquitin ligase in carcinogenesis and adipogenic differentiation [18,19].…”