OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma Pedro P. Medina,Mona Nolde& Frank J. Slack
MicroRNAs (miRNAs) belong to a recently discovered class of small RNA molecules that regulate gene expression at the post-transcriptional level. miRNAs have crucial functions in the development and establishment of cell identity, and aberrant metabolism or expression of miRNAs has been linked to human diseases, including cancer1. Components of the miRNA machinery and miRNAs themselves are involved in many cellular processes that are altered in cancer, such as differentiation, proliferation and apoptosis. Some miRNAs, referred to as oncomiRs2, show differential expression levels in cancer and are able to affect cellular transformation, carcinogenesis and metastasis, acting either as oncogenes or tumour suppressors. The phenomenon of ‘oncogene addiction’ reveals that despite the multistep nature of tumorigenesis, targeting of certain single oncogenes can have therapeutic value3, 4, and the possibility of oncomiR addiction has been proposed but never demonstrated3. MicroRNA-21 (miR-21) is a unique miRNA in that it is overexpressed in most tumour types analysed so far. Despite great interest in miR-21, most of the data implicating it in cancer have been obtained through miRNA profiling and limited in vitro functional assays. To explore the role of miR-21 in cancer in vivo, we used Cre and Tet-off technologies to generate mice conditionally expressing miR-21. Here we show that overexpression of miR-21 leads to a pre-B malignant lymphoid-like phenotype, demonstrating that mir-21 is a genuine oncogene. When miR-21 was inactivated, the tumours regressed completely in a few days, partly as a result of apoptosis. These results demonstrate that tumours can become addicted to oncomiRs and support efforts to treat human cancers through pharmacological inactivation of miRNAs such as miR-21.
Nature：对oncomiRs上瘾的肿瘤
发布时间：2010-09-03 00:00 文章来源： 作者：
miRNA是调控基因表达、在确定细胞身份中起重要作用的小RNA分子，它们被与人类癌症联系了起来，在人类癌症中，它们被称为“oncomiRs”。关于癌症形成的一个模型认为，增值的细胞变得对激发某个致癌基因中的突变“上瘾”，而且也曾有人提出，肿瘤也会变得依赖于“oncomiRs”。
现在，用小鼠（研究人员通过基因工程方法使这些小鼠表达微RNA-21 (miR-21)，该微RNA迄今为止在所分析过的大多数肿瘤类型中都过度表达）所做研究表明，miR-21诱导pre-B-cell淋巴瘤；在没有它的情况下，恶性细胞发生凋亡和退化，正如按它们对其存在“上瘾”（的假设）所预期的那样。因此，“oncomiR-21”和其他类似 miRNA的药理灭活应有治疗效果。
Nature doi:10.1038/nature09284
OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma
Pedro P. Medina,Mona Nolde& Frank J. Slack
MicroRNAs (miRNAs) belong to a recently discovered class of small RNA molecules that regulate gene expression at the post-transcriptional level. miRNAs have crucial functions in the development and establishment of cell identity, and aberrant metabolism or expression of miRNAs has been linked to human diseases, including cancer1. Components of the miRNA machinery and miRNAs themselves are involved in many cellular processes that are altered in cancer, such as differentiation, proliferation and apoptosis. Some miRNAs, referred to as oncomiRs2, show differential expression levels in cancer and are able to affect cellular transformation, carcinogenesis and metastasis, acting either as oncogenes or tumour suppressors. The phenomenon of ‘oncogene addiction’ reveals that despite the multistep nature of tumorigenesis, targeting of certain single oncogenes can have therapeutic value3, 4, and the possibility of oncomiR addiction has been proposed but never demonstrated3. MicroRNA-21 (miR-21) is a unique miRNA in that it is overexpressed in most tumour types analysed so far. Despite great interest in miR-21, most of the data implicating it in cancer have been obtained through miRNA profiling and limited in vitro functional assays. To explore the role of miR-21 in cancer in vivo, we used Cre and Tet-off technologies to generate mice conditionally expressing miR-21. Here we show that overexpression of miR-21 leads to a pre-B malignant lymphoid-like phenotype, demonstrating that mir-21 is a genuine oncogene. When miR-21 was inactivated, the tumours regressed completely in a few days, partly as a result of apoptosis. These results demonstrate that tumours can become addicted to oncomiRs and support efforts to treat human cancers through pharmacological inactivation of miRNAs such as miR-21.
转自：生物谷