MicroRNA profiling with correlation to gene expression revealed the oncogenic miR-17-92 cluster to be up-regulated in osteosarcoma
MicroRNA profiling with correlation to gene expression revealed the oncogenic miR-17-92 cluster to be up-regulated in osteosarcoma
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DOI：
10.1016/j.cancergen.2012.03.001
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发表时间：
2012-05-01
期刊：
影响因子：
1.9
通讯作者：
Nathrath, Michaela
中科院分区：
文献类型：
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作者：
Baumhoer, Daniel;Zillmer, Stephanie;Nathrath, Michaela
骨肉瘤是遗传上复杂的肿瘤，具有丰富的结构和数量变化。然而，该病的分子发病机制仍然知之甚少。除了各种癌基因和肿瘤抑制基因之外，已知失调的microRNAs（miRNAs）影响肿瘤的发展和生物学。因此，我们研究了六种成熟的骨肉瘤细胞系（HOS 58，U2-OS，Saos-2，MNNG/HOS，SJSA-1和MG-63）的全基因组miRNA表达（miRBase Version 15.0，http：//www.mirbase.org/），并将我们的发现与基因表达相关联。将培养的成骨细胞（hFOB 1.19）和间充质干细胞（L 87/4）用作正常参考。仅关注在大多数骨肉瘤细胞系中失调的miRNA，我们鉴定了几种具有致癌和肿瘤抑制特性的miRNA，包括致癌miR-17-92簇的各种成员。此外，在骨肉瘤细胞系中，发现参与分化（RGMB，LRRC 17），细胞周期控制（CCNE 1）和凋亡（LIMA 1，CAMK 2N 1）的几个基因被失调，最有可能是由于miRNA表达模式的改变。我们的研究结果表明，在骨肉瘤的基因表达的连续变化，这有力地表明致病和潜在的治疗意义的失调的miRNA的关键影响。
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.