MiR-381 And MiR-489 Suppress Cell Proliferation And Invasion By Targeting CUL4B Via The Wnt/?-Catenin Pathway In Gastric Cancer

Accumulating evidence has highlighted the critical role of cullin 4B(CUL4B)in driving tumorigenesis in several malignancies,including gastric cancer(GC);however,the mechanisms underlying CUL4 B upregulation remain unclear.The dysregulation of microRNAs(miRNAs or miRs)is known to be involved in tumorigenesis.In this study,we report that the expression of miR-381 and miR-489 is downregulated and is negatively correlated with that of CUL4 B in GC tissues and cell lines.Further analysis verified that miR-381 and miR-489 directly targeted CUL4 B.CUL4B silencing inhibited cell proliferation,migration and invasion by inactivating the Wnt/?-catenin pathway.miR-381/miR-489 overexpression recapitulated the effects of CUL4 B silencing,while CUL4 B restoration negated the suppressive effects induced by the ectopic expression of miR-381/miR-489.Furthermore,miR-381/ miR-489 exerted tumour suppressive functions by inactivating the Wnt/?-catenin pathway through the targeting of CUL4 B.Taken together,the findings of this study suggest that the miR-381/miR-489-mediated expression of CUL4 B modulates the proliferation and invasion of GC cells via the Wnt/?-catenin pathway,which indicates that the miR-381/miR-489-CUL4 B axis is critical in the control of GC tumorigenesis.