The Function And Mechanism Study Of Intestinal Epithelial Cell Biological Rhythm In Colorectal Cancer

Colorectal cancer(CRC)is one of the common malignant tumors in the digestive system,and its high morbidity and mortality pose a serious threat to human health.There are many causes of colorectal cancer,and the pathogenesis is complicated.In recent years,with the deepening of research on colorectal cancer,some progress has been made in colorectal cancer surgery and chemotherapy,but the research on the pathogenesis of colorectal cancer and early prevention and treatment methods are still limited.Therefore,it is necessary to conduct a more in-depth study on the pathogenesis and early prevention and treatment of colorectal cancer,to clarify the principles of environmental risk factors,and to provide a new theoretical system for the prevention,diagnosis and treatment of colorectal cancer.Although epidemiological studies have shown that long-term circadian rhythms dysfunction may lead to higher rates of tumors,further direct experimental evidence is needed to confirm.The relationship between circadian rhythm disorder and the development of colorectal cancer is particularly weak,and the mechanism is very unclear.It is urgent to conduct in-depth research.By analyzing the expression level of Bmal1 gene in human colorectal cancer specimens,we confirmed that the expression of Bmal1 in colorectal cancer tissues was lower than the normal tissues in the same patient,and the expression level of Bmal1 was positively correlated with the survival rate of patients.These evidences suggest that the circadian rhythm of the intestinal may play a key role in the development of colorectal cancer.For this purpose,we generated a knockout mouse that specifically knocks out the Bmall gene in the intestinal epithelium and found that there was no significant effect on the intestinal homeostasis.Subsequently,we generated a mouse model of induced and spontaneous colorectal cancer,and found that the number and size of tumors were significantly up-regulated in Bmall gene knockout mice.The mechanism studies showed that the cell proliferation in Bmall knockout tumors did not change but cell apoptosis was significantly inhibited.In addition,there was no significant change in p53 protein expression,and the activity of Stat3 protein and S6 protein increased significantly,indicating that Bmall regulation of p53-independent and p-stat3 and p-s6-regulated apoptosis processes are involved in the development of colorectal cancer.Our studies analyze the correlation between the biological rhythm genes Bmall and the development and progression of colorectal cancer,being hopeful to provide new methods for prevention,diagnosis and treatment of colorectal cancer.