Profiling non-coding RNA levels with clinical classifiers in pediatric Crohn’s disease

Abstract

Background Crohn’s disease (CD) is a heritable chronic inflammatory disorder. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation by affecting gene expression, but can also directly affect protein function, thus having a substantial impact on biological processes. We investigated whether non-coding RNAs (ncRNA) at diagnosis are dysregulated during CD at different CD locations and future disease behaviors to determine if ncRNA signatures can serve as an index to outcomes. Methods Using subjects belonging to the RISK cohort, we analyzed ncRNA from the ileal biopsies of 345 CD and 71 non-IBD controls, and ncRNA from rectal biopsies of 329 CD and 61 non-IBD controls. Sequence alignment was done (STAR package) using Human Genome version 38 (hg38) as reference panel. The differential expression (DE) analysis was performed with EdgeR package and DE ncRNAs were identified with a threshold of fold change (FC) > 2 and FDR < 0.05 after multiple test corrections. Results In total, we identified 130 CD specific DE ncRNAs (89 in ileum and 41 in rectum) when compared to non-IBD controls. Similarly, 35 DE ncRNAs were identified between B1 and B2 in ileum, whereas no differences among CD disease behaviors were noticed in rectum. We also found inflammation specific ncRNAs between inflamed and non-inflamed groups in ileal biopsies. Overall, we observed that expression of mir1244-2, mir1244-3, mir1244-4, and RN7SL2 were increased during CD, regardless of disease behavior, location, or inflammatory status. Lastly, we tested ncRNA expression at baseline as potential tool to predict the disease status, disease behaviors and disease inflammation at 3-year follow up. Conclusions We have identified ncRNAs that are specific to disease location, disease behavior, and disease inflammation in CD. Both ileal and rectal specific ncRNA are changing over the course of CD, specifically during the disease progression in the intestinal mucosa. Collectively, our findings show changes in ncRNA during CD and may have a clinical utility in early identification and characterization of disease progression.

Cell-autonomous Hedgehog signaling controls Th17 polarization and pathogenicity

“…9c and Supplementary Fig. 13a ) in ulcerative colitis patients compared to healthy controls 32 , 33 . Interestingly, in the setting of human ulcerative colitis, expression levels of Hedgehog components positively correlated with the expression levels of key Th17 markers such as IL17A and CCR6 (Fig.…”

“…The human datasets are from publicly available data were obtained from GEO with the following accession numbers: GSE49877 , GSE109142, and GSE117993 . The cited references provide details of participant characteristics and relevant ethics/consent guidelines applied 31 – 33 . Number and sex of participants are indicated in the Source Data.…”

The transcriptomic landscape of monosomy X (45,X) during early human fetal and placental development

“…The potential role of OVCH1-AS1 is not known. Recent studies have suggested different expression levels of leukocyte OVCH1-AS1 in relation to frailty with age in humans 34 , as well as higher OVCH1-AS1 expression in biopsies from Crohn's disease 53 .…”

“…The potential role of OVCH1-AS1 is not known. Recent studies have suggested different expression levels of leukocyte OVCH1-AS1 in relation to frailty with age in humans 34 , as well as higher OVCH1-AS1 expression in biopsies from Crohn’s disease 53 . Furthermore, several studies have identified OVCH1-AS1 as a higher-expressed gene in leukocytes, fat, and muscle from adult women 19,20,24,27,41 .…”

Expression profiles of the lncRNA antisense GAS5-AS1 in colon biopsies from pediatric inflammatory bowel disease patients and its role in regulating sense transcript GAS5

“…Noteworthy, lncRNAs are differentially expressed in IBD, suggesting their influence on the course of inflammation [ 12 , 13 ]. For instance, the lncRNA growth arrest-specific transcript 5 (GAS5), one of the most studied, is downregulated in inflamed colonic tissues of pediatric patients with IBD and modulates the expression of the matrix metalloproteinases (MMPs) 2 and 9, involved in the pathogenesis of IBD [ 14 ].…”