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Clinical Trial
. 2017 Nov 28;23(44):7888-7898.
doi: 10.3748/wjg.v23.i44.7888.

Circulating miR-125a but not miR-125b is decreased in active disease status and negatively correlates with disease severity as well as inflammatory cytokines in patients with Crohn's disease

Chen-Ming Sun  1 , Jie Wu  2 , Heng Zhang  1 , Gan Shi  1 , Zhi-Tao Chen  1
Affiliations
Clinical Trial

Circulating miR-125a but not miR-125b is decreased in active disease status and negatively correlates with disease severity as well as inflammatory cytokines in patients with Crohn's disease

Chen-Ming Sun et al. World J Gastroenterol. .

Abstract

Aim: To determine the association of circulating miR-125a/b expression with the risk and disease severity of Crohn's disease (CD), and with inflammatory cytokines.

Methods: Plasma samples were collected from patients with active CD (A-CD), or CD in remission (R-CD) and from healthy controls (HCs). The levels of the inflammatory cytokines interleukin-17 (IL-17), tumour necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay. The expression of miR-125a/b was assessed by quantitative polymerase chain reaction (qPCR).

Results: Twenty-nine A-CD patients, 37 R-CD patients, and 37 HCs were included in the study. Plasma miR-125a expression was decreased in A-CD patients compared with that in R-CD patients (P < 0.001) and HCs (P < 0.001). miR-125a expression levels enabled the differentiation of A-CD from R-CD patients [area under curve (AUC) = 0.854] and from HCs (AUC = 0.780), whereas miR-125b expression did not. miR-125a was negatively correlated with C-reaction protein (CRP) (P = 0.017), erythrocyte sedimentation rate (ESR) (P = 0.026), Crohn's disease activity index (CDAI) (P = 0.003), IL-17 (P = 0.015), and TNF-α (P = 0.004) in A-CD patients. Furthermore, miR-125a was negatively associated with CRP (P = 0.038) and CDAI (P = 0.021) in R-CD patients. Regarding miR-125b, no association with CRP, CDAI, IL-17, TNF-α, or IFN-γ was found in A-CD or in R-CD patients. miR-125a levels gradually increased in A-CD patients who achieved clinical remission (P = 0.009) after 3-mo treatment, whereas they remained unchanged among patients who failed to achieve remission. No changes in miR-125b expression were detected in remission or non-remission patients after treatment.

Conclusion: Circulating miR-125a but not miR-125b is decreased in patients with active disease status and negatively correlates with disease severity and inflammatory cytokines in patients with CD.

Keywords: Crohn’s disease; Disease risk; Disease severity; Inflammatory cytokines; miR-125.

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Conflict of interest statement

Conflict-of-interest statement: The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
miR-125a/b expression in active Crohn's disease patients, patients with Crohn's disease in remission, and healthy controls. miR-125a was decreased in A-CD patients compared with R-CD patients and HCs (A), while no differences in miR-125b were detected between groups. Comparison between two groups was performed by the Wilcoxon signed-rank test. P < 0.05 was considered significant. A-CD: Active Crohn's disease; R-CD: Crohn's disease in remission; HCs: Healthy controls.
Figure 2
Figure 2
Receiver operating characteristic curve analysis of miR-125a/b for prediction of active Crohn's disease patients and patients with Crohn's disease in remission. Receiver operating characteristic curve was operated to assess miR-125a/b expression in differentiating A-CD patients from R-CD patients and from HCs. miR-125a was able to differentiate A-CD patients from R-CD (A) patients and from HCs (B), whereas miR-125b was not (A, B). Neither miR-125a nor miR-125b could differentiate R-CD from HCs (C). A-CD: Active Crohn's disease; R-CD: Crohn's disease in remission; HCs: Healthy controls.
Figure 3
Figure 3
Correlations of miR-125a/b expression with disease severity in active Crohn's disease patients. A-C: Correlations of miR-125a expression with disease severity in A-CD patients; D-F: Correlations of miR-125b expression with disease severity in A-CD patients. Spearman’s test was used to analyse the correlation of miR-125a/b expression with disease severity. P < 0.05 was considered significant. A-CD: Active Crohn's disease; R-CD: Crohn's disease in remission; HCs: Healthy controls.
Figure 4
Figure 4
Correlations of miR-125a/b expression with disease severity in patients with Crohn's disease in remission. A-C: Correlations of miR-125a expression with disease severity in R-CD patients; D-F: Correlations of miR-125b expression with disease severity in R-CD patients. Spearman’s test was used to analyse the correlation of miR-125a/b expression with disease severity. P < 0.05 was considered significant. A-CD: Active Crohn's disease; R-CD: Crohn's disease in remission; HCs: Healthy controls.
Figure 5
Figure 5
Correlations of miR-125a/b expression with inflammatory cytokines in active Crohn's disease patients. A-C: Correlations of miR-125a expression with inflammatory cytokines in A-CD patients; D-F: Correlations of miR-125b expression with inflammatory cytokines in A-CD patients. Spearman’s test was used to analyse the correlation of miR-125a/b expression with inflammatory cytokines. P < 0.05 was considered significant. A-CD: Active Crohn's disease; R-CD: Crohn's disease in remission; HCs: Healthy controls.
Figure 6
Figure 6
Correlations of miR-125a/b expression with inflammatory cytokines in patients with Crohn's disease in remission. A-C: Correlations of miR-125a expression with inflammatory cytokines in R-CD patients; D-F: Correlations of miR-125b expression with inflammatory cytokines in R-CD patients. Spearman’s test was used to analyse the correlation of miR-125a/b expression with inflammatory cytokines. P < 0.05 was considered significant. A-CD: Active Crohn's disease; R-CD: Crohn's disease in remission; HCs: Healthy controls.
Figure 7
Figure 7
miR-125a/b expression in active Crohn's disease patients after treatment. After 3-mo treatment, miR-125a expression was increased in A-CD patients who achieved clinical remission but remained stable in patients who failed to achieve remission. Conversely, no changes in miR-125b expression were observed in either remission or non-remission patients after 3-mo treatment. Comparison between visits in the same group was performed by the Wilcoxon signed-rank test. P < 0.05 was considered significant. A-CD: Active Crohn's disease.
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