The Role of Long Noncoding RNAs in Intestinal Health and Diseases: A Focus on the Intestinal Barrier

Abstract

The gut is the body's largest immune organ, and the intestinal barrier prevents harmful substances such as bacteria and toxins from passing through the gastrointestinal mucosa. Intestinal barrier dysfunction is closely associated with various diseases. However, there are currently no FDA-approved therapies targeting the intestinal epithelial barriers. Long noncoding RNAs (lncRNAs), a class of RNA transcripts with a length of more than 200 nucleotides and no coding capacity, are essential for the development and regulation of a variety of biological processes and diseases. lncRNAs are involved in the intestinal barrier function and homeostasis maintenance. This article reviews the emerging role of lncRNAs in the intestinal barrier and highlights the potential applications of lncRNAs in the treatment of various intestinal diseases by reviewing the literature on cells, animal models, and clinical patients. The aim is to explore potential lncRNAs involved in the intestinal barrier and provide new ideas for the diagnosis and treatment of intestinal barrier damage-associated diseases in the clinical setting.

Keywords: biomarkers; diseases; function; intestinal barrier; lncRNAs.

Figure 1

The biogenesis and function of lncRNAs. (A) Biogenesis of lncRNA: Lncrnas are weakly transcriptionally spliced, resulting in partial retention in the nucleus. Most lncRNAs are exported to the cytoplasm via NXF1. (B) Functions of lncRNAs in the nucleus: In the nucleus, lncRNAs interact with DNA to form an RNA/DNA hybrid or interact with chromatin-modifying enzymes, thereby affecting the chromatin modification state. LncRNAs also regulate the functions of promoters and enhancers of target genes, resulting in the enhancement or inhibition of the expression of parental genes or other genes. (C) Functions of lncRNAs in the cytoplasm. In the cytoplasm, lncRNAs can participate in posttranscriptional regulation by interacting with different RBPs, microRNAs, and mRNAs. RBP: RNA-binding proteins; RNAPII: RNA polymerase II.

Figure 2

Effects of lncRNAs on the intestinal barrier. (A) LncRNAs in gut microbial barrier: The injury factors lead to intestinal dysbiosis, thus affecting the expression of lncRNA. (B) LncRNAs in intestinal chemical barrier: LncRNAs (H19) affect the thickness of the intestinal mucus layer by influencing mucin secretion. (C) LncRNAs in intestinal physical barrier: On the one hand, lncRNAs can exert an influence on the damage and repair of intestinal stem cells, Paneth cells, goblet cells, and epithelial cells (Uc.173, WiNTRLINC1, LncGata6, H19). On the other hand, lncRNAs can affect cell–cell junctions (Uc.173, SPRY4-1T1). (D) LncRNAs in intestinal immune barrier: LncRNAs can regulate the intestinal immune balance by influencing the polarization of macrophages (NEAT1, LncRNA-Cox2), the secretion of cytokines (TMC3-AS1, MALAT1), the proliferation and differentiation of epithelial cells and dendritic cells, and the activation of T cells (IFNG-AS1, Lnc-ITSN1-2, DQ786243).