Abstract
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.
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Data Availability
Data sets during the current study are available from the corresponding author on reasonable request.
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Yan Wang, Nan Wang, Lianlian Cui, Yan Li, and Yanbo Cheng searched the literature and designed the study. All the authors performed the experiments, analyzed the data, and wrote the manuscript. Yan Wang and Yanbo Cheng revised the manuscript.
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Wang, Y., Wang, N., Cui, L. et al. Long Non-coding RNA MEG3 Alleviated Ulcerative Colitis Through Upregulating miR-98-5p-Sponged IL-10. Inflammation 44, 1049–1059 (2021). https://doi.org/10.1007/s10753-020-01400-z
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DOI: https://doi.org/10.1007/s10753-020-01400-z