Functional studies on micro RNAs (miRNAs)
| First author | Study model | miRNA of interest | mRNA/pathway target | Findings |
|---|---|---|---|---|
| Nguyen144 | AIEC infection in T84 cells and mouse enterocytes. Translational studies in ileal CD biopsies | miR-30C and miR-130A | ATG5 ATG16L1 | Adherent Escherichia coli upregulate miRNAs, reduce levels of ATG5 and ATG16L1 and inhibit autophagy |
| Zhai145 | Jurkat T cells Colonic epithelial cells | miR-142-3p | ATG16L1 | Reduced ATG16L1 mRNA and protein levels, regulating autophagy in CD. |
| Lu146 | HCT116, SW480, HeLa and U2OS cell lines. Colonic biopsies from CD and healthy controls | miR106B, miR93 | ATG16L1 | Reduced levels of ATG16L1 and autophagy |
| Brest10 | HEK-293 cells Colonic biopsies | miR-196 | IRGM | A risk variant of IRGM alters the binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in CD |
| Brain9 | Dendritic cell line, miR-29 KO murine models | miR-29 | IL-12p40 (direct target) IL-12p19 (indirect target) | NOD2 induces miR-29 release and limits IL- 23 release NOD2 polymorphism alters the expression of miR-29 and contributes to pathogenesis in CD. |
| Xue147 | IL-10 KO mice MyD88 KO mice RAG KO mice Murine dendrite cells | miR-10a | IL-12/IL-23p40 | miR-10a expression is regulated by the intestinal microbiota and targets the Th17 pathway. This miRNA may play a role in intestinal homoeostasis |
| Koukos148 | HCT-116 colonocyte cells, murine models and colonic biopsies from patients with UC | miR-124 | STAT3 | Downregulation of miR-124 results in proinflammatory response in UC |
| Shi5 Yang149 | miR-21 KO DSS model and wild type mouse models Caco-2 cells, colonic biopsies from UC and healthy controls | mir-21 | RhoB | miR-21 is overexpressed in inflammation and tissue injury. miR-21 KO improves survival in DSS colitis mouse model Targeting RhoB impairs the tight junction integrity and decreases transepithelial resistance and increases inulin permeability |
| Nata150 | IL-10 deficient mice | miR-146b | siah2 | miR-146b improves intestinal inflammation and epithelial barrier by activating NFκB |
| Chuang92 | HCT116 colonic epithelial cells | miR-192, miR-495, miR-512, miR-671 | NOD2 | Downregulates NOD2 expression, suppresses NFκB, inhibits IL8 and CXCL3 expression |
| Chen151 | Intestinal epithelial cells Intestinal biopsies | miR-200b | TGFβ | miR-200b promotes the growth of intestinal epithelial cells by inhibiting epithelial-mesenchymal transition via TGFβ |
| Feng152 | UC intestinal biopsies HCT116 cells HT29 cells | miR-126 | IκBα | Promotes NFκB mediated inflammation by targeting IκBα, a known inhibitor of the NFκB pathway. |
| Nguyen153 | Caco2-BBE cells Mouse epithelial cells Colonic CD tissues | miR-7 | CD98 expression | miR-7 regulates the expression of CD98. CD98 expression upregulated and miR-7 decreased in actively inflamed CD tissues. |
| Singh123 | miR-155 KO mice | miR-155 | Th17 pathway | miR-155 KO mice models and demonstrated that these mice are protected from experimental colitis compared with wild type mice. |
| Wu8 | miR-21 KO TNBS and T cell transfer model of colitis miR-21 KO DSS colitis model | miR-21 | Th1 pathway | miR-21 KO results in reduced DSS induced colitis but exacerbated inflammation in TNBS and T cell transfer model of colitis |
AIEC, adherent invasive Escherichia coli; CD, Crohn's disease; DSS, dextran sulfate sodium; IL, interleukin; IRGM, immunity related GTPase family M protein; KO, knockout; miR, microRNA; NFκB, nuclear factor-κB; NOD2, nuclear oligomerisation domain-containing protein 2; TGFβ, transforming growth factor β; TNBS, trinitrobenzene sulfonic acid.