Systematic analysis and characterization of long non-coding RNA genes in inflammatory bowel disease

Abstract

The cases of inflammatory bowel disease (IBD) are increasing rapidly around the world. Due to the multifactorial causes of IBD, there is an urgent need to understand the pathogenesis of IBD. As such, the usage of high-throughput techniques to profile genetic mutations, microbiome environments, transcriptome and proteome (e.g. lipidome) is increasing to understand the molecular changes associated with IBD, including two major etiologies of IBD: Crohn disease (CD) and ulcerative colitis (UC). In the case of transcriptome data, RNA sequencing (RNA-seq) technique is used frequently. However, only protein-coding genes are analyzed, leaving behind all other RNAs, including non-coding RNAs (ncRNAs) to be unexplored. Among these ncRNAs, long non-coding RNAs (lncRNAs) may hold keys to understand the pathogenesis of IBD as lncRNAs are expressed in a cell/tissue-specific manner and dysregulated in a disease, such as IBD. However, it is rare that RNA-seq data are analyzed for lncRNAs. To fill this gap in knowledge, we re-analyzed RNA-seq data of CD and UC patients compared with the healthy donors to dissect the expression profiles of lncRNA genes. As inflammation plays key roles in the pathogenesis of IBD, we conducted loss-of-function experiments to provide functional data of IBD-specific lncRNA, lung cancer associated transcript 1 (LUCAT1), in an in vitro model of macrophage polarization. To further facilitate the lncRNA research in IBD, we built a web database, IBDB (https://ibd-db.shinyapps.io/IBDB/), to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in IBD patients compared with healthy donors.

The role of long non-coding RNA in Crohn's disease

“…They possess the capability to modulate the expression of pro-inflammatory cytokines, including TNF-α [ 52 ] and IL-6, IL-1β, and IL-12 [ 47 ]. LncRNAs such as LUCAT1 have been shown to regulate the activation and polarization of macrophages, which play a crucial role in the inflammatory process [ 24 ].…”

“…LUCAT1, an inflammatory regulator, exhibits significantly increased expression in the intestinal tissues of CD patients compared to healthy individuals [ 24 ]. Elevated LUCAT1 expression is associated with disease severity and progression [ 25 ], and it plays a crucial role in transitioning patients with CD from the remission phase to the active phase, as observed in both clinical and endoscopic assessments.…”