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Objective To investigate the expression of miR-21 in renal clear cell carcinoma and its clinical significance as well as how miR-21 regulates the proliferation and apoptosis of 786-O renal clear cell carcinoma cell line through regulating programmed cell death 4 (PDCD4). Methods By analyzing the data of renal clear cells cancer in The Cancer Genome Atlas (TCGA) database, we compared the expression of miR-21 in renal cancer tissues and adjacent normal tissues and explored the differences in miR-21 level in renal cancer at different clinicopathological stage, T stage, N stage and M stage. We also analyzed the association between miR-21 level and survival of patients by Kaplan-Meier method and Log-rank test. 786-O cells were transfected with AS-miR-21 to deplete miR-21. MTT assay and flow cytometry were applied to measure cell proliferation and apoptosis, respectively. We then measured the mRNA and protein levels of PDCD4 in 786-O cells depleted for miR-21 by qRT-PCR and Western blot, respectively, and performed a dual-luciferase assay to detect the direct regulation of PDCD4 by miR-21. Results Expression of miR-21 was significantly higher in renal cancer tissues than in adjacent tissues (P<0.0001). The expression levels of miR-21 at stage Ⅲ and stage Ⅳ renal cancer were significantly higher than that at stage Ⅰ (both P<0.0001). Moreover, miR-21 expression was positively correlated with clinicopathological stages of renal cancer by correlation analysis (r=0.262, P<0.0001). The correlation test indicated that miR-21 level was also positively correlated with T stage of renal cancer (r=0.250, P<0.0001), lymph node metastasis (N1) and distant metastasis (all P<0.0002). Patients with high miR-21 expression had significantly shorter median survival time than those with low miR-21 expression (Log-rank P<0.001). Compared with control cells, 786-O cells depleted for miR-21 showed significantly decreased cell proliferation (P<0.05) and increased cell apoptosis rate (P=0.005). PDCD4 mRNA (P=0.002) and protein levels were significantly elevated in 786-O cells with down-regulated miR-21 levels. In addition, the dual-luciferase reporter assay showed that the relative luciferase intensity of PDCD4 reporter in cells transfected with AS-miR-21 was significantly higher than that of control cells (P=0.003). Conclusion miR-21 expression was up-regulated in renal cancer and correlated with clinicopathological stage and survival of patients. miR-21 promoted 786-O cell proliferation and inhibited apoptosis probably through regulating PDCD4 expression. These results indicate that miR-21 plays an important role in formation and development of renal cancer. [ABSTRACT FROM AUTHOR]