Ulcerative colitis (UC) is a refractory chronic colitis disease with the particularly complex cause. Recently, long noncoding RNAs (lncRNAs) have been reported to be related to the development of UC. LncRNA MEG3 has been proved to play an anti-inflammatory role in a variety of inflammatory diseases, which share similar pathogenesis with UC, indicating the potential involvement of lncRNA MEG3 in UC. This study aims to investigate the functional role and underlying mechanism of lncRNA MEG3 in UC. Gradient concentration of H₂O₂ (0, 20, 50, 100, and 200 μM) was used to induce Caco-2 damage models in vitro. Cell viability was detected by cell counting kit-8 (CCK-8) assay. LncRNA MEG3, miR-98-5p, and IL-10 levels in H₂O₂₋treated Caco-2 cells were assessed by performing real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, the binding relationship between lncRNA MEG3 and miR-98-5p, as well as the binding relationship between miR-98-5p and IL-10, was validated using dual-luciferase reporter assay. 2, 4, 6-Trinitrobenzenesulfonic acid solution (TNBS) was applied to induce ulcerative colitis in young rats. The body weight, disease activity index (DAI), length and weight of the colons, pathological scores of UC rats, reactive oxygen species (ROS), and inflammatory cytokines were determined to evaluate the effects of lncRNA MEG3 on the progression of UC. Besides, hematoxylin-eosin (HE) staining was exploited to observe histological changes of UC rat colons. In addition, western blotting analysis was also performed to evaluate the apoptosis and pyroptosis-related protein levels. Moreover, lncRNA MEG3, miR-98-5p, and IL-10 levels in UC rat colons were further assessed by RT-qPCR. Meanwhile, IL-10 expression was determined using immunohistochemistry. LncRNA MEG3 and IL-10 levels were distinctly decreased while miR-98-5p was increased in Caco-2 damage models and UC rats. Bioinformatics analysis predicted the binding sites of lncRNA MEG3 to miR-98-5p and miR-98-5p to IL-10. Besides, dual-luciferase reporter assay validated the negative correlation between lncRNA MEG3 and miR-98-5p, miR-98-5p, and IL-10. Overexpressed lncRNA MEG3 reduced. DAI scores and colon weight/length ratio improved UC ulceration. In addition, upregulation of lncRNA MEG3 relieved oxidative stress, inflammatory response, apoptosis, and pyroptosis of UC rat colons. LncRNA MEG3 overexpression alleviates the serve ulceration of UC rat colons by upregulating IL-10 expression via sponging miR-98-5p. To sum up, this study reveals the protective role of lncRNA MEG3 in the development of UC and may provide potential therapeutic targets for UC.

溃疡性结肠炎 (UC) 是一种难治性慢性结肠炎疾病，病因特别复杂。最近，有报道长链非编码 RNA（lncRNA）与 UC 的发生发展有关。LncRNA MEG3 已被证明在多种炎症性疾病中发挥抗炎作用，其发病机制与 UC 相似，表明 lncRNA MEG3 可能参与 UC。本研究旨在探讨lncRNA MEG3在UC中的功能作用和潜在机制。H ₂ O _{2 的}梯度浓度（0、20、50、100 和 200 μM）用于体外诱导 Caco-2 损伤模型。通过细胞计数试剂盒-8 (CCK-8) 测定法检测细胞活力。H ₂ O _{2− 中的}LncRNA MEG3、miR-98-5p 和 IL-10 水平通过进行实时定量聚合酶链反应 (RT-qPCR) 来评估处理过的 Caco-2 细胞。此外，lncRNA MEG3 与 miR-98-5p 之间的结合关系，以及 miR-98-5p 与 IL-10 之间的结合关系，使用双荧光素酶报告基因检测进行了验证。应用 2, 4, 6-三硝基苯磺酸溶液 (TNBS) 诱导幼鼠溃疡性结肠炎。测定体重、疾病活动指数（DAI）、结肠长度和重量、UC大鼠病理评分、活性氧（ROS）和炎症细胞因子，评价lncRNA MEG3对UC进展的影响。此外，利用苏木精-伊红（HE）染色观察UC大鼠结肠的组织学变化。此外，还进行了蛋白质印迹分析以评估细胞凋亡和细胞焦亡相关的蛋白质水平。此外，通过 RT-qPCR 进一步评估了 UC 大鼠结肠中的 lncRNA MEG3、miR-98-5p 和 IL-10 水平。同时，使用免疫组织化学确定IL-10的表达。在 Caco-2 损伤模型和 UC 大鼠中，LncRNA MEG3 和 IL-10 水平明显降低，而 miR-98-5p 水平升高。生物信息学分析预测了 lncRNA MEG3 与 miR-98-5p 和 miR-98-5p 与 IL-10 的结合位点。此外，双荧光素酶报告基因检测验证了 lncRNA MEG3 与 miR-98-5p、miR-98-5p 和 IL-10 之间的负相关性。过表达的 lncRNA MEG3 减少。DAI 评分和结肠重量/长度比改善了 UC 溃疡。此外，lncRNA MEG3 的上调减轻了氧化应激、炎症反应、细胞凋亡、和 UC 大鼠结肠的焦亡。LncRNA MEG3过表达通过上调IL-10表达减轻UC大鼠结肠溃疡通过海绵 miR-98-5p。综上所述，本研究揭示了 lncRNA MEG3 在 UC 发展中的保护作用，可能为 UC 提供潜在的治疗靶点。