Long noncoding RNA uc.230/CUG-binding protein 1 axis sustains intestinal epithelial homeostasis and response to tissue injury.

Autor:	Yu TX; Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Kalakonda S; Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Liu X; Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Han N; Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Chung HK; Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Xiao L; Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA., Rao JN; Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA., He TC; Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois, USA., Raufman JP; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.; Department of Medicine and., Wang JY; Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.; Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2022 Oct 10; Vol. 7 (19). Date of Electronic Publication: 2022 Oct 10.
DOI:	10.1172/jci.insight.156612
Abstrakt:	Intestinal epithelial integrity is commonly disrupted in patients with critical disorders, but the exact underlying mechanisms are unclear. Long noncoding RNAs transcribed from ultraconserved regions (T-UCRs) control different cell functions and are involved in pathologies. Here, we investigated the role of T-UCRs in intestinal epithelial homeostasis and identified T-UCR uc.230 as a major regulator of epithelial renewal, apoptosis, and barrier function. Compared with controls, intestinal mucosal tissues from patients with ulcerative colitis and from mice with colitis or fasted for 48 hours had increased levels of uc.230. Silencing uc.230 inhibited the growth of intestinal epithelial cells (IECs) and organoids and caused epithelial barrier dysfunction. Silencing uc.230 also increased IEC vulnerability to apoptosis, whereas increasing uc.230 levels protected IECs against cell death. In mice with colitis, reduced uc.230 levels enhanced mucosal inflammatory injury and delayed recovery. Mechanistic studies revealed that uc.230 increased CUG-binding protein 1 (CUGBP1) by acting as a natural decoy RNA for miR-503, which interacts with Cugbp1 mRNA and represses its translation. These findings indicate that uc.230 sustains intestinal mucosal homeostasis by promoting epithelial renewal and barrier function and that it protects IECs against apoptosis by serving as a natural sponge for miR-503, thereby preserving CUGBP1 expression.
Databáze:	MEDLINE
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