MicroRNAs (miRNAs or miR) serve as oncogenes and tumor suppressors. In a previous study, it was revealed that has-miRNA-429 (miR-429) is a tumor suppressor in 786-O renal cell carcinoma (RCC) cells. However, its mechanism in RCC remains to be determined. The present study aimed to explain the functional role and mechanism of miR-429 in RCC pathogenesis. Luciferase reporter assays demonstrated that miR-429 overexpression reduced the transcriptional activity of AKT serine/threonine kinase 1 (AKT1). Reverse transcripton-quantitative (RT-q) PCR and western blot analysis indicated that the mRNA and protein expression of AKT1 was downregulated in 786-O RCC cell lines when miR-429 was overexpressed, indicating that miR-429 may directly target AKT1 in RCC. Therefore, miR-429 overexpression enhanced the inhibition of tumor size and weight in nude mice in vivo. The current study indicated that the novel miR-429-regulated pathway may provide insights into RCC oncogenesis and metastasis. [ABSTRACT FROM AUTHOR]