LncRNA TUG1 regulates the balance of HuR and miR-29b-3p and inhibits intestinal epithelial cell apoptosis in a mouse model of ulcerative colitis
LncRNA TUG1 regulates the balance of HuR and miR-29b-3p and inhibits intestinal epithelial cell apoptosis in a mouse model of ulcerative colitis
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DOI：
10.1007/s13577-020-00428-5
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发表时间：
2020-10
期刊：
影响因子：
4.3
通讯作者：
Yuxi Tian;Ying Wang;Fujun Li;Junwen Yang;Yan Xu;Ouyang Miao
中科院分区：
文献类型：
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作者：
Yuxi Tian;Ying Wang;Fujun Li;Junwen Yang;Yan Xu;Ouyang Miao
本研究旨在探讨长链非编码RNA（lncRNA）牛磺酸上调蛋白1（TUG 1）在溃疡性结肠炎（UC）发病中的作用及其机制。通过暴露于右旋糖酐硫酸钠（DSS）诱导小鼠UC模型。用TNF-α处理结肠上皮YAMC细胞，模拟肠上皮细胞（IEC）的炎症环境。RNA pull-down和RIP分析TUG 1和HuR之间的相互作用。荧光素酶活性测定法检测TUG 1与miR-29 b-3 p的相互作用。MTT法检测细胞增殖;流式细胞术和Western blot分析凋亡相关蛋白来评估细胞凋亡。TUG 1过表达促进TNF-α刺激的YAMC细胞增殖，抑制细胞凋亡。分子机制分析表明，TUG 1通过与HuR相互作用，正向调节HuR/c-myc轴，导致c-myc表达上调;同时，TUG 1通过与miR-29 b-3 p结合，负向调节miR-29 b-3 p/CDK 2信号通路，导致CDK 2表达去抑制。进一步的动物实验表明，TUG 1过表达减弱了DSS诱导的小鼠UC的进展。总体而言，TUG 1通过调节HuR和miR-29 b-3 p的平衡来抑制IEC凋亡和UC进展。
This study aimed to investigate the role of long non-coding RNA (lncRNA) taurine up-regulated 1 (TUG1) in the development of ulcerative colitis (UC) and to explore the underlying mechanisms. A murine model of UC was induced by dextran sodium sulfate (DSS) exposure. The colonic epithelial YAMC cells were treated with TNF-α to simulate the inflammatory environment of intestinal epithelial cells (IECs). RNA pull-down and RIP assays were performed to analyze the interaction between TUG1 and HuR. Luciferase activity assay was conducted to evaluate the interaction between TUG1 and miR-29b-3p. Cell proliferation was evaluated by MTT assay. Cell apoptosis was assessed by flow cytometry and western blot analysis of apoptosis-related proteins. TUG1 overexpression promoted cell proliferation and inhibited cell apoptosis in the TNF-α-stimulated YAMC cells. The mechanistic analysis showed that TUG1 positively regulated the HuR/c-myc axis via its interaction with HuR, leading to upregulation of c-myc expression; meanwhile, TUG1 negatively regulated the miR-29b-3p/CDK2 signaling via binding to miR-29b-3p, leading to derepression of CDK2 expression. Further animal experiments showed that TUG1 overexpression attenuated UC progression in the DSS-induced UC in mice. Collectively, TUG1 inhibits IEC apoptosis and UC progression by regulating the balance of HuR and miR-29b-3p.