Distinct transcriptomic signature of mRNA and microRNA in ulcerative colitis and irritable bowel syndrome

ABSTRACT Background Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both chronic bowel diseases involving stress. To identify genes differentially expressed in UC and IBS, and to determine whether psychological stress can influence those gene expressions, we conducted this pilot study. Methods Patients of UC, irritable bowel syndrome (IBS) and normal controls (NC) (n=5 in each group) were recruited. Perceived stress scale (PSS) was adopted to assess psychological stress level. Sigmoid mucosa samples were collected during colonoscopy. Differentially expressed genes (DEGs) of both mRNA and microRNA (DEG-mRNA and DEG-miRNA) were identified by RNA-Seq and microarray, respectively. Weighted gene co-expression network analysis (WGCNA), gene ontology, and microRNA target analysis were performed to identify regulatory relationships and pathways involved. Pearson correlation was performed to identify the relationship between DEGs and PSS score. Results In total, 1,770 and 938 DEG-mRNAs, 107 and 3 DEG-miRNAs were identified in UC and IBS (nominal P<0.05), respectively. The transcriptome changes in UC and IBS were highly correlated but transcriptome severity was larger in UC. There were 268 overlapped DEG-mRNAs and 3 overlapped DEG-miRNAs between UC and IBS. Median PSS score was 27.5 (24.7, 40.0) in UC, 27.0 (17.5, 32.5) in IBS and 22.0 (12.0, 28.5) in NC. Five of the UC’s DEG-mRNAs were significantly correlated to PSS scores, including SLC4A7, PLCB1, SPATA33, DECR2, RP11-792A8.4. There were no DEGs correlate with PSS scores in IBS. One module enriched for immunological pathways was upregulated in UC. Metabolic pathways were enriched in IBS. Within the UC-related co-expression module, we identified 18 DEG-mRNAs that were also targets of DEG-miRNA. Conclusions Integration of microRNA and mRNA expression profiles identified changes of gene expression in both UC and IBS. Although the two diseases have significant overlapped transcriptomic changes, they have distinct signature. Immunological pathways are involved prominently in UC while metabolic pathways in IBS. Psychological stress is uniquely associated with the transcriptome changes of UC.