Construction of microRNA–messenger networks for human osteosarcoma

Osteosarcoma is the most common bone tumor in children and young adults. Although the microRNAs (miRNA) expression analyses of osteosarcoma have been performed previously, the construction of miRNA–messenger RNA (mRNA) networks for osteosarcoma is needed. This study aimed to identify osteosarcoma‐related miRNAs through analyzing the microarray datasets and to construct the regulatory network of miRNA–mRNA for human osteosarcoma. The datasets were extracted from the Gene Expression Omnibus and the differentially expressed miRNAs were screened through the limma package in Bioconductor. Genes targeted by the differentially expressed miRNAs were screened out by using the Miranda, MirTarget2, PicTar, PITA, and TargetScan databases. The predicted target genes were further analyzed by Gene Ontology and pathway enrichment analysis and a regulatory network of differentially expressed miRNAs and their target osteosarcoma‐associated genes was constructed. A total of 36 downregulated miRNAs and 182 upregulated miRNAs were identified in osteosarcoma samples compared with normal samples and 397 target genes for upregulated miRNAs and 222 target genes for downregulated miRNAs were obtained. The enriched pathways for target genes of differentially expressed miRNAs included transcriptional misregulation in cancer, the AMPK signaling pathway, and MAPK signaling pathway. In the regulatory network, has‐miR‐199a‐5p targeted the highest number of genes and nemo‐like kinase (NLK) was targeted by five miRNAs (hsa‐miR‐140‐5p, hsa‐miR‐107, hsa‐miR‐324‐5p, hsa‐miR‐199a‐5p, and hsa‐miR‐28‐5p). The has‐miR‐324‐5p targets NLK, TGFB2, and PPARG. These miRNAs and their target genes may serve as potential therapeutic targets of osteosarcoma. In short, our study carried out comprehensive bioinformatics analysis and determined 36 downregulated and 182 upregulated miRNAs in osteosarcoma samples compared with normal control samples. Analysis of differentially expressed miRNAs and their target genes showed that the‐miR 140‐5p, hsa‐miR 107, hsa‐miR 324‐5p, hsa‐miR 199a‐5p, and hsa‐miR 28‐5p targeted NLK. miR‐324‐5p targeted NLK, TGFB2, and PPARG. Therefore, these miRNAs may contribute to the pathogenesis of osteosarcoma and be potential therapeutic targets.