Inhibition of miR-106a/b Modulates Autophagy-Related Gene Expression in the ULK1–Beclin-1–ATG12 Axis in Experimental Colitis

Abstract

This study investigated the role of miR-106a and miR-106b in autophagy in a dextran sulfate sodium (DSS)-induced colitis model. DSS induced experimental colitis in Wistar rats, divided into control, DSS-induced-colitis, DSS + AntimiR-106a, DSS + AntimiR-106b, and DSS + scrambled miRNA groups. Disease severity was assessed by Disease Activity Index (DAI) and histopathology, while miR-106a/b and autophagy-related genes (ULK1, Beclin-1, ATG12) were measured in blood and colon by RT-qPCR. DAI and histological scores differed significantly among the five experimental groups (Kruskal–Wallis test, p < 0.001 and p < 0.001, respectively). Post-hoc analysis showed that DSS administration significantly increased both DAI and histological injury scores compared with the control group. In blood samples, miR-106a and miR-106b expression levels were significantly higher in the DSS group than in controls, with 17.46-fold ( p < 0.001) and 12.56-fold ( p = 0.012) increases, respectively, whereas ULK1, Beclin-1, and ATG12 expression showed a non-significant decreasing trend. In the AntimiR-106a group, circulating miR-106a expression was lower than both pre-treatment levels and the DSS group by 167-fold ( p = 0.001) and 3.1-fold ( p = 0.040), respectively. This group also showed higher blood ULK1 and Beclin-1 expression compared with the DSS group by 10.2-fold ( p = 0.016) and 1.9-fold ( p = 0.012), respectively. In the AntimiR-106b group, circulating miR-106b expression was lower after administration than pre-treatment levels by 7.5-fold ( p = 0.005), while ULK1 and Beclin-1 expression levels were higher than in the DSS group by 8.85-fold ( p = 0.031) and 1.88-fold ( p = 0.011), respectively. In colon tissue, ULK1, Beclin-1, and ATG12 expression levels were significantly higher in the AntimiR-106a group than in the DSS group by 19.4-fold ( p = 0.022), 14.0-fold ( p = 0.018), and 6.4-fold ( p = 0.042), respectively. Similarly, the AntimiR-106b group showed higher colon tissue ULK1, Beclin-1, and ATG12 expression than the DSS group by 7.6-fold ( p = 0.018), 5.8-fold ( p = 0.019), and 4.5-fold ( p = 0.006), respectively. Scrambled miRNA administration was not associated with significant histological improvement or a consistent autophagy-related transcriptional response. Inhibition of miR-106a/b was associated with increased autophagy-related gene expression and partial improvement in disease-related clinical and histological indices in DSS-induced experimental colitis. These findings suggest that the miR-106 family may be involved in the transcriptional regulation of autophagy-related pathways in intestinal inflammation.