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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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Abstract

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.

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Funding

This study was supported by grants from the National Natural Science Foundation of China (Nos. 81800471, 81974065).

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Authors and Affiliations

  1. Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Yuxi Tian

  2. Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, No. 87, Xiangya Road, Changsha, Hunan, China

    Ying Wang, Fujun Li, Junwen Yang & Miao Ouyang

  3. Department of Health Care Center, Xiangya Hospital, Central South University, Changsha, No. 87, Xiangya Road, Changsha, Hunan, China

    Yan Xu

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  1. Yuxi Tian
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Correspondence to Yan Xu or Miao Ouyang.

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Supplementary Figure 1. (A) Relative TUG1 expression in YAMC cells transfected with si-NC, si-TUG1-1, si-TUG1-2, and si-TUG1-3 was examined by qRT-PCR analysis. (B) Relative HuR expression in YAMC cells transfected with si-NC, si-HuR-1, si-HuR-2, and si-HuR-3 was examined by qRT-PCR analysis. (C) TUG1 expression in the intestine after injection of LV-TUG1 as compared to LV-Ctrl (n=6 per group). **P<0.01, vs. si-NC or LV-Ctrl. Data represent the mean ± standard deviation from three independent experiments

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Tian, Y., Wang, Y., Li, F. et al. LncRNA TUG1 regulates the balance of HuR and miR-29b-3p and inhibits intestinal epithelial cell apoptosis in a mouse model of ulcerative colitis. Human Cell 34, 37–48 (2021). https://doi.org/10.1007/s13577-020-00428-5

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  • DOI: https://doi.org/10.1007/s13577-020-00428-5

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