P101 RNA-SEQ ANALYSIS OF MOUSE MODELS OF COLITIS IDENTIFIES NOVEL MRNA AND LNCRNA TARGETS ASSOCIATED WITH HUMAN INFLAMMATORY BOWEL DISEASE

Abstract

Inflammatory bowel disease (IBD) is a complex disorder that is associated with significant morbidity. While many advances have been made in the recent past with new diagnostic and therapeutic tools, a deeper understanding of its basic pathophysiology is needed to continue this trend towards improving treatments. A new area of research is now focusing on aspects of gene regulation from previously uninvestigated portions of the genome, namely long noncoding RNAs (lncRNAs). These new players have been implicated in a variety of cell processes including cell-cycle control, embryonic development, and inflammation. However, their role in IBD has yet to be fully determined. By utilizing an unbiased, high-throughput transcriptomic analysis of two well-established mouse models of colitis, we set out to uncover novel coding and non-coding RNAs that are differentially expressed in the setting of colonic inflammation. RNA-seq analysis was performed using colonic tissues from the dextran sodium sulfate (DSS)-induced model and a genetic model in mice lacking IL-10. We identified 81 coding RNAs that were commonly altered in both experimental models. Of these coding RNAs, 12 of the human orthologs were differentially expressed in a transcriptomic analysis of IBD patients including Ubiquitin D. Our analysis also identified 13 non-coding RNAs that were differentially expressed in either the DSS or the IL10 -/- model. Surprisingly, only three non-coding RNAs were commonly dysregulated in both of these models. Additionally, we identified linc-EPS as a differentially expressed non-coding RNA in the IL10-/- model of colitis and its putative human ortholog, TTC39-AS1. The discovery of new coding and non-coding RNAs such as Ubiquitin D and TTC39-AS1 expands our transcriptional knowledge of mouse models of IBD and offers additional targets to deepen our understanding of its pathophysiology.