Specific Plasma MicroRNA Signatures in Predicting and Confirming Crohn's Disease Recurrence: Role and Pathogenic Implications

Abstract

INTRODUCTION: MicroRNAs (miRNAs) are important epigenetic regulators in Crohn's disease (CD); however, their contribution to postoperative recurrence (POR) is still unknown. We aimed to characterize the potential role of miRNAs in predicting POR in patients with CD and to identify their pathogenic implications. METHODS: Of 67 consecutively operated patients with CD, we included 44 with pure ileal CD. Peripheral blood samples were taken before surgery and during follow-up. The patients were classified according to the presence or absence of POR assessed by ileocolonoscopy or magnetic resonance imaging enterography. The miRNAs were profiled by reverse transcription polymerase chain reaction before surgery and during morphological POR or, for those who remained in remission, 1 year after surgery. R software and mirWalk were used. RESULTS: Five human miRNAs (miR-191-5p, miR-15b-5p, miR-106b-5p, miR-451a, and miR-93-5p) were selected for discriminating between the 2 patient groups at presurgery (PS), with an area under the curve of 0.88 (95% confidence interval [0.79, 0.98]). Another 5 (miR-15b-5p, miR-451a, miR-93-5p, miR-423-5p, and miR-125b-5p) were selected for 1 year, with an area under the curve of 0.96 (95% confidence interval [0.91, 1.0]). We also created nomograms for POR risk estimation. CCND2 and BCL9L genes were related to PS miRNA profiles; SENP5 and AKT3 genes were related to PS and 1 year; and SUV39H1 and MAPK3K10 were related to 1 year. DISCUSSION: Different plasma miRNA signatures identify patients at high POR risk, which could help optimize patient outcomes. We developed nomograms to facilitate the clinical use of these results. The identified miRNAs participate in apoptosis, autophagy, proinflammatory immunological T-cell clusters, and reactive oxygen species metabolism.

Identifying hub genes and miRNAs in Crohn’s disease by bioinformatics analysis

“…It has been shown that elevated levels of miR-21-5p in the stool of IBD patients could be a guide for the noninvasive clinical diagnosis of IBD ( Zhou et al, 2021b ). It has been demonstrated that miR-93-5p is upregulated before surgery and downregulated in relapsed CD patients ( Moret-Tatay et al, 2021 ). Wang et al found that the lncRNA MEG3 could improve ulcerative colitis by upregulating miR-98-5p-Sponed IL-10 ( Wang et al, 2021 ).…”

Immunoepigenetic Regulation of Inflammatory Bowel Disease: Current Insights into Novel Epigenetic Modulations of the Systemic Immune Response

“…They share analogous characteristics, such as intermittent, chronic, and/or progressive inflammation and features specific to each such as transmural inflammation of the gastrointestinal wall (from the mouth to the anus) in CD and inflammation limited to the colon and rectal mucosa in UC [ 5 ]. Although the etiopathogenesis of IBD remains unknown, the disease appears to be a dysregulated immune response to unknown triggers in genetically predisposed patients [ 6 ].…”

“…Due to its complexity, it is an interesting factor that needs to be explored in detail in other specific reviews. On the other hand, noncoding RNAs, especially microRNAs, represent the most studied epigenetic mechanism in IBD, and many reviews have dealt with this topic [ 6 , 19 ]. Therefore, we have focused on describing in detail other more novel and less studied epigenetic mechanisms in IBD.…”

MicroRNA and granulocyte‐monocyte adsorption apheresis combotherapy after inadequate response to anti‐TNF agents in ulcerative colitis

“…4 Recent molecular research has shown that between the epigenetic mechanisms, microRNAs (miRNAs) emerge as important factors in the physiopathology of IBD. 1,5 miRNAs are evolutionarily conserved, endogenous, single-stranded, non-coding RNAs that bind to the 3 0 untranslated region (UTR), 5' UTR, or partially translated region of a target mRNA, which usually inhibit mRNA expression. 1 MiRNAs play an important biological role as regulators of cell function and homeostasis, so their impaired activities are linked to disease, as is the case for UC.…”