SMAD4 and renal cell carcinoma: To further dissect the mechanism underlying miR-452-5p modulating induction of RCC metastasis, we searched for potential downstream genes of miR-452-5p through four different miRNA target-predicting algorithms including TargetMiner, miRTarBase, miRWalk and miRTar, then focused on the one possible candidate target gene SMAD4 (Fig. 4a).