The MiR-17-5p/STAT3/IL-17A Mediates The Occurrence And Development Of Colitis-associated Colorectal Cancer

Objective To investigate the possible molecular mechanism in the development of colitis associated colorectal cancer(CAC)in mice induced by dextran sodium sulfate(DSS)and induced by azoxymethane/dextran sodium sulfate(AOM/DSS).In order to provide theoretical basis for the diagnosis and treatment of CAC and the study of effective molecular target drugs of CAC.Methods(1)Animal models of colitis and CAC were established by azoxymethane/dextran sodium sulfate(AOM/DSS)and DSS.Life status,body weight and stool status of animal models were observed during the animal were treatmented with AOM/DSS or DSS.(2)The length of the colorectal of mice in each group was measured and the morphological changes of the colorectal epithelial cells were observed by hematoxylin-eosin(HE)staining.(3)Immunohistochemistry,Western Blot(WB)and Reverse transcription quantitative polymerase chain reaction(q RT-PCR)were used to detect the expression levels of CD44,CD105,ki-67,ERK and P-ERK in the colorectal tissues of mice in each group.(4)q RT-PCR or PCR was used to detect the expression levels of inflammatory factors such as IL-1β,TNF-α and NLRP3 in the colorectal tissues of mice in each group.(5)Immunohistochemistry,WB,PCR or q RT-PCR were used to detect the expression levels of IL-17 A,P-STAT3 and NF-κB in the colorectal tissues of mice in each group.(6)expression levels of mi R-17-5p and STAT3 in colorectal tissues of mice in each group were detected by q RT-PCR.Results(1)Animal models of colitis and CAC were successfully established by AOM/DSS and DSS.(2)The expression levels of inflammatory factors such as IL-1β,TNF-α and NLRP3 in colorectal tissues of mice in the cancer model group and inflammatory model group increased,and the expression levels of inflammatory factors such as IL-1β,TNF-αand NLRP3 in colorectal tissues of mice in the cancer model group were higher than that in colon tissues of mice in the inflammatory model group.(3)The expression levels of P-STAT3,IL-17 A and NF-κB in colorectal tissues of mice in the cancer model group and inflammatory model group increased,and the expression levels of P-STAT3,IL-17 A and NF-κBin colorectal tissues of mice in the cancer model group were higher than that in colon tissues of mice in the inflammatory model group.(4)Mi R-17-5p in each expression in colorectal tissue of mice and negatively correlated with the expression of STAT3,namely mi R-17-5p in cancer and inflammation in model mice model group mice colorectal tissue of the expression level is reduced,and mi R-17-5p in the tissue of colorectal cancer group mice expression level is lower than of mice inflammation expression level in colorectal tissue.Conclusion CAC induced by AOM/DSS may through the mi R-17-5p mediated STAT3/IL-17A/NF-κB signaling pathway.