Synergistic action of the microRNA-17 polycistron and Myc in aggressive cancer development.

来自 EBSCO

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作者：

H Tagawa，K Karube，S Tsuzuki，K Ohshima，M Seto

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摘要：

The c13orf25/miR-17 cluster, which is responsible for 13q31-q32 amplification in malignant lymphoma, contains the microRNA-17-18-19-20-92 polycistron. A previous study demonstrated that this polycistron could modulate tumor formation following transplantation of microRNA 17-19b into Eu-myc mice. Another study reported that Myc can upregulate the miR-17 cluster by binding directly upstream of the miR-17 locus. These findings suggest that Myc and the miR-17 cluster synergistically contribute to cancer development. In the study presented here, we observed recurrent 13q31-32 amplification in MYC -rearranged lymphomas (11 of 47 cases). Quantitative real-time polymerase chain reaction analysis of c13orf25 for MYC -rearranged lymphomas demonstrated that cases with 13q31-32 amplification showed significantly higher expression of c13orf25 than cases without such amplification, although cases without 13q31-32 amplification still showed slight upregulation of c13orf25. To investigate the relationship between Myc and the miR-17 polycistron in tumorigenesis, we engineered rat fibroblasts (Rat-1) that constitutively express the miR-17 polycistron (miR), Myc, or both miR and Myc. The highest level of miR expression was detected in Rat-1 transfected with both miR and Myc, whereas Myc transfectant cells alone also showed slight upregulation of miR. Furthermore, we demonstrated that nude mice injected with Rat-1 transfected with both miR and Myc presented more accelerated tumor growth than those injected with Myc transfectant cells. These results suggest that miR is stably upregulated in the presence of constitutive expression of Myc, and that the deregulation of miR and Myc synergistically contribute to aggressive cancer development, probably by repressing tumor suppressor genes. ( Cancer Sci 2007; 98: 14821490)

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关键词：

Caisson assembly for tritium safety study Reynolds equation Detritiation system

DOI：

10.1111/j.1349-7006.2007.00531.x

被引量：

264

年份：

2010