Novel Molecular Characteristics of Ulcerative Colitis

Abstract

Ulcerative Colitis (UC) is a chronic autoimmune inflammatory disease and one type of inflammatory bowel disease (IBD). UC is characterized by a temporal course of remission and relapse. Environmental factors, immune system dysregulation, and genetic susceptibility interact intricately in the aetiology of UC. It is unclear how interactions involving non-coding RNAs (ncRNAs), epigenetic modifications, and genetic changes relate to active UC, remission, and relapse. The inability to predict relapse in patients with UC poses a challenge to current treatment options. Visible disease manifestations, which are usually absent in patients in remission, frequently place limitations on the use of clinical diagnostic methods. Thus, it is necessary to characterize remission at the molecular level. To investigate the molecular mechanisms in remission and active UC, data from whole transcriptome sequencing (RNA-seq) and whole genome bisulfite sequencing (WGBS) of mucosal biopsies have been analysed with a variety of bioinformatic methods The analyses resulted in the identification of a set of mitochondrial RNAs and small nuclear RNAs (snoRNAs) which may influence the duration of remission. Several identified remission-specific genes are involved in pro- and anti-inflammatory pathways and some of the identified genes may be regulated by DNA methylation. In addition, several DNA-methylated long non-coding RNAs (lncRNAs) have been found to be involved in UC inflammatory immune responses. These findings might shed light on the pathophysiology of UC and suggest new diagnostic markers.