MicroRNA-30b-5p Functions As A Metastasis Suppressorin Colorectal Cancer By Targeting Rap1b

Background and objective:Colorectal cancer(CRC)is one of the most common malignant tumors in the digestive system.Liver metastasis(LM)is the leading cause of death in patients with CRC,and it is also the key point and obstacle in CRC treatment.The study found that miR-30b-5p is involved in the regulation of tumor metastasis,but its relationship with LM of CRC is still unclear.Methods and results:Here,we investigated the role and molecular mechanism of miR-30b-5p in LM of CRC.We constructed miR-30b-5p overexpressing HCT116 and Lo Vo cells with lentivirus and found that the migration and invasion ability of CRC cells was significantly decreased after overexpression of miR-30b-5p,cell-matrix adhesion and movement were blocked.The expression of related proteins such as Zeb1,Snail,p-Paxillin and p-Src is decreased.Bioinformatics analysis revealed that miR-30b-5p targets Rap1 b,and we used dual luciferase reporter experiments to confirm that Rap1 b is a downstream target gene of miR-30b-5p.After overexpression of Rap1 b in cells overexpressing miR-30b-5p,cell migration and invasion were restored,and adhesion and motility were enhanced.Rap1 b knocking down significantly inhibited migration and invasion of CRC cells,constructed a shrunken cell morphology,and decreased the cell motility capacity,which were consistent with the results of miR-30b-5p overexpression.In vivo experiments showed that miR-30b-5p overexpressing inhibited LM of CRC cells,and Rap1 b attenuated the inhibitory effect of miR-30b-5p.In addition,we used q PCR,WB and IHC to find that the expression of miR-30b-5p in tumor tissue of CRC patient was significantly lower than that in its adjacent tissue and was further decreased in LM tissue.While Rap1 b expression was observed increased in the tumor and LM tissues.The expression of the two is negatively correlated.Conclusion:These results not only indicate that miR-30b-5p inhibits the invasion and metastasis of CRC cells by downregulating Rap1 b expression but also provide a new target for the treatment of LM from CRC.