Identification and validation of microRNAs and their targets expressed in osteosarcoma.

Osteosarcoma (OS) is the most common type of bone cancer in children and adolescents, and has a poor prognosis. Previous studies have demonstrated that a number of microRNAs (miRNAs) were deregulated in OS, and that the expression of certain miRNAs was correlated with the stage of OS. Therefore, miRNAs may serve a role as a diagnostic and prognostic biomarker of OS. miRNA and mRNA integrated analysis of public expression profiles in the Gene Expression Omnibus database for OS was performed, and the regulated targets of miRNA in OS were predicted. Next, the regulatory network of miRNAs/genes was constructed and verified by reverse transcription-quantitative polymerase chain reaction in tissues and MG-63 cell lines. Two miRNA expression profiling studies and four eligible mRNA expression profiling studies were selected. Ten upregulated miRNAs, 5 downregulated miRNAs and 5 DGEs were identified in OS compared with normal tissues. hsa-miR-346 was inversely correlated with the target gene c-FLIP, which was consistent with the results of integrated analysis. In vitro, pre-miRNA-346 can downregulate the protein expression of c-FLIP, while not changing the mRNA level of c-FLIP. In the regulatory network, hsa-miR-346 and its target gene, c-FLIP, can be used as biomarkers for an earlier diagnosis of OS.