The Role And Mechanism Of Circular RNA ERBIN Promotes Growth And Metastasis Of Colorectal Cancer By MiR-125a-5p/miR-138-5p/4EBP-1axis

The incidence and mortality of colorectal cancer(CRC)have been increasing year by year in the world.Colorectal cancer has become one of the main causes of death in cancer worldwide.Circular RNA(circRNA)is a new type of non-coding RNA,which has high stability and tissue specificity.Recently,circRNAs have draw a lot of attention for the important role in the occurrence and development of many kinds of tumors.CircRNAs,which have a negative regulatory effects on miRNAs,have been proved to be microRNA sponge and affect the occurrence and development of colorectal cancer by participating the multiple tumor related signal pathways.Erbin is a member of a superfamily of proteins with LRR and PDZ domains.It is expressed specifically and abundantly in epithelial cells.Recently,Erbin has been shown to play an important role in the transportation,maintenance of epithelial cell polarity and cell tight junction.Several studies including ours have demonstrated that Erbin is involved in CRC.Based on our previous study,we found that circ-ERBIN,which is formed by the circularization of 2-4 exons of ERBIN,was highly expressed in different human and mouse tissues,and significantly increased in more aggressive CRC cells.In order to further explore the role of circ-ERBIN in the development of CRC,we conducted a series of animal experiments and in-vitro experiments.The results showed that overexpression of circ-ERBIN promotes the proliferation,invasion and metastasis of CRC.On the contrary,circ-ERBIN knockdown inhibits the growth and metastasis of colorectal cancer.Furthermore,the expression of circ-ERBIN is higher in CRC tissues compared to their counterpart surrounding tissues.Mechanistecally,we found that circ-ERBIN,which is mostly located in the cytoplasm,functions as a miRNA sponge to decrease the inhibition of miR-125a-5p and miR-138-5p on the downstream target gene 4EBP-1 and promote the proliferation,invasion and metastasis of CRC.Altogether,we demonstrated here that circ-ERBIN promotes the proliferation,invation and metastasis of CRC by targeting miR-125a-5p/miR-138-5p axis and thus synergistically increases the expression of eIF4E-binding protein 1(4EBP-1).Most importantly,our study suggests that circ-ERBIN is a new tumor marker and treatment target for clinical diagnosis of CRC.