MicroRNA profiling with correlation to gene expression revealed the oncogenic miR-17-92 cluster to be up-regulated in osteosarcoma

Abstract

Osteosarcomas are genetically complex tumors with abundant structural and numerical alterations. The molecular pathogenesis of the disease is, however, still poorly understood. Aside from various oncogenes and tumor suppressor genes, deregulated microRNAs (miRNAs) are known to influence tumor development and biology. We therefore investigated six well-established osteosarcoma cell lines (HOS58, U2-OS, Saos-2, MNNG/HOS, SJSA-1, and MG-63) for genome-wide miRNA expression (miRBase Version 15.0, http://www.mirbase.org/) and correlated our findings with gene expression. Cultured osteoblasts (hFOB 1.19) and mesenchymal stem cells (L87/4) were used as normal references. Focusing only on miRNAs that were deregulated in the majority of osteosarcoma cell lines, we identified several miRNAs with oncogenic and tumor suppressor properties, including various members of the oncogenic miR-17-92 cluster. In addition, several genes involved in differentiation (RGMB, LRRC17), cell cycle control (CCNE1), and apoptosis (LIMA1, CAMK2N1) were found to be deregulated in osteosarcoma cell lines, most likely due to altered miRNA expression patterns. Our findings indicate a crucial impact of deregulated miRNAs with consecutive changes in gene expression in osteosarcomas, which strongly suggests pathogenetic and potentially therapeutic implications.