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Background: Clear cell renal cell carcinoma (ccRCC), as the commonest type among renal cell cancers, is featured with easy relapse and metastasis. Despite mounting achievements on its treatment and diagnosis, the identification of new biomarkers remains urgent. Purposes: Present study aimed to explore the role of microRNA-4429 (miR-4429) in ccRCC. Methods: The expression of miR-4429 and cyclin-dependent kinase 6 (CDK6) was evaluated by real-time polymerase chain reaction and Western blot. Cell proliferation, migration and invasion was evaluated by MTT and transwell assays. The interaction between miR-4429 and CDK6 was assessed by luciferase reporter assay. Prognostic significance of miR-4429 was evaluated by Kaplan-Meier analysis. Correlation between miR-4429 and CDK6 was determined by Spearman's correlation analysis. Results: Firstly, the downregulation of miR-4429 and upregulation of CDK6 in ccRCC tissues and cells were uncovered by quantitative real-time polymerase chain reaction. The prognostic significance of miR-4429 in ccRCC patients was proved by Kaplan-Meier analysis. Gain- and loss-of-function assays validated the suppressive effect of miR-4429 on cell proliferation, migration, invasion, as well as epithelial-mesenchymal transition (EMT) progression. The interaction between miR-4429 and CDK6 was predicted by bioinformatics tool and confirmed by luciferase reporter assay. And the negative expression correlation between miR-4429 and CDK6 was verified by Spearman's correlation analysis. Rescue assays confirmed the role of miR-4429/CDK6 in proliferation, metastasis and EMT progression in ccRCC. Conclusions: Present study revealed that miR-4429 suppressed ccRCC tumor progression and EMT by targeting CDK6. [ABSTRACT FROM AUTHOR]