Functional elucidation of MiR-34 in osteosarcoma cells and primary tumor samples. MiR-34s have been characterized as direct p53 targets, which induce apoptosis, cell cycle arrest, and senescence. MiR-34s were found to associate with tumorigenesis. Thus far, there is no study on the role of MiR-34s in osteosarcoma. In the current study, we intensively investigated the function of MiR-34s in two osteosarcoma cell lines: U2OS (p53(+/+)) and SAOS-2 (p53(-/-)). We found that MiR-34s affect the expression of its target genes partially in a p53-dependent manner. And p53 also partially contributes to the MiR-34s induced cell cycle arrest and apoptosis. Finally, we examined the expression, genetic and epigenetic alterations of MiR-34 gene in 117 primary osteosarcoma samples. Expression of MiR-34s was decreased in tumor samples, and MiR-34 genes underwent minimal deletions and epigenetic inactivation in osteosarcomas.