Huangqi Baizhu decoction prevents CAC process by inhibiting MIR-31-5p/STAT3 positive circle / 中国药理学通报

ABSTRACT

To explore the role of miR-31-5p/STAT3 in the pathogenesis of colitis-assosiated cancer (CAC) and the intervention mechanism of Huangqi Baizhu decoction. Methods The CAC model of C57BL/6 mice was established by AOM/DSS method. The differential expression of MicroRNA in control and CAC mice was detected. qPCR was used to screen differential MicroRNAs; Western blot was used to detect the expression levels of STAT3 , p-STAT3 and IL-6Ra. Results AOM was injected into abdominal cavity once, combined with 3% DSS free drinking for three cycles to establish model. After eight weeks, moderate and/or severe dysplasia of colonic mucosa appeared in model mice. After detection, the expression of miR-31-5p and STAT3 and p-STAT3 proteins significantly increased. After intervention with Huangqi Baizhu decoction, the expressions of miR-31-5p and STAT3 and p-STAT3 proteins were down-regulated. In vitro, miR-31-5p over-expression in RAW264. 7 by transfect method, and the expression of STAT3 protein increased significantly compared with that of control. On the other hand, stimulated by IL-6 or TNF-a for 24 h, miR-31-5p levels were up-regulated significantly, suggesting that inflammatory factors could cause a positive correlation between miR-31-5p/STAT3. At the same time, ATRII + AST (atractylodesin II + astragaloside) mixture significantly down-regulated miR-31-5p, STAT3, IL-6Ra increase induced by IL-6 stimulation. Conclusions miR-31-5p/STAT3 forms a positive feedback loop, which plays an important role in the pathogenesis of CAC. miR-31-5p/STAT3 may continue to amplify the inflammation effect and eventually lead to the dysplasia of colonic epithelium and even tumorigenesis.