MiRNA-155 Promotes Proliferation And Invasion Of Colorectal Cancer Cells By Regulating The Wnt/?-Catenin

Colon cancer is one of the most common malignant tumors in the digestive tract.Its incidence is increasing year by year,and the overall prognosis is poor.Many kinds of microRNAs have been found to play the role of oncogene or tumor suppressor gene in colorectal malignant tumors.In recent years,the popLular nicroRNA-155 is closely related to the etiology,clinical manifestations and prognosis of colon cancer.The application of microRNA 155 in the diagnosis,treatment and prevention of tumors has a good effect.However,the mechanism and pathway of the role of microRNA 155 in colon cancer are not clear.Wnt/beta-Catenin signal transduction pathway plays an important ro:le in the early stage of colon cancer.At the same time,the most common signal transduction process in colon cancer is activated by Wnt pathway.The purpose of this study is to explore the role of microRNA155 in colon cancer and its mechanism in the proliferation and invasion of colon cancer cells and find its target.Methods:l.Real-time fluorescence quantitative qPCR and/or Northern blot to detect the expression of microRNA-155 in colon cancer,adjacent normal tissues and cell lines2.The expression of Wnt/beta-Catenin signal transduction pathway related target genes(CD44,Axin 2 and LGR5)and the expression of cell proliferation markers Ki-67.,HBP1,beta-Catenin were detected in the cell lines transfected with anti-microRNA-155 or microRNA-155 mimic.MTT and Transwell experiments were also carried out.3.Predict the possible target genes of microRNA-155 by using bioinformatics online database.4.The target gene HBP1 of microRNA-155 was validated by qPCR and/or Western blot.5.Establishment of transplanted colon cancer model and liver metastasis model in nude mice to understand the effect of microRNA155 on proliferation and invasion of colon cancer.Results:I.RT-PC.R and Northern blot showed that the expression of microRNA-155 in colorectal cancer tissues was significantly higher than that in adjacent normal tissues.At the same time,the expression level of microRNA-155 in colorectal cancer cell lines was significantly higher than that in normal colon epithelial cells2.The proliferation of colon cancer cells transfected with anti-microRNA-155 decreased significantly,and the expression of target genes related to beta-Catenin,HBPI,Wnt/beta-Catenin pathway(CD44,Axin 2 and LGR5)was inhibited,as well as the growth of transplanted colon cancer in nude mice.3.The expression of beta-Catenin in colon cancer cells transfected with microRNA-155 mimic increased and the invasiveness of the cells increased significantly.At the same time,it could promote the liver metastasis ability of the tumors in nude mice.The re-transfection of beta-Catenin siRNA showed that it could reverse the invasiveness of microRNA-155 mimic to cells and the liver metastasis rate of nude mice.4.Bioinformatics method identified HBP1 as the target of microRNA-155 and mediated Wnt/beta-Catenin signaling pathway.Conclusion:High expression of microRNA-155 can promote the growth and metastasis of colon cancer.It may be involved in the proliferation and invasion of colon cancer through activation of Wnt/beta-Catenin signal transduction pathway mediated by HBP1.The results show that microRNA155 can be used as a tumor marker and provide new ideas and evidence for individualized treatment of colorectal cancer.It may also be a promising drug for clinical treatment of colorectal cancer.