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OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma

机译：MicroRNA-21诱导的前B细胞淋巴瘤的体内模型中的OncomiR成瘾

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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 cancer. 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 oncomiRs, 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 value, and the possibility of oncomiR addiction has been proposed but never demonstrated. 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.
机译：MicroRNA（miRNA）属于最近发现的一类小RNA分子，它们在转录后水平上调节基因表达。 miRNA在细胞身份的发展和确立中具有至关重要的功能，miRNA的异常代谢或表达已与人类疾病（包括癌症）联系在一起。 miRNA机制的组件和miRNA本身参与了许多在癌症中改变的细胞过程，例如分化，增殖和凋亡。一些被称为oncomiRs的miRNA在癌症中表现出不同的表达水平，并且能够作为致癌基因或抑癌基因，影响细胞转化，致癌性和转移。 “致癌基因成瘾”现象表明，尽管肿瘤发生过程具有多步骤性质，但靶向某些单一致癌基因仍具有治疗价值，并且已经提出了致癌成瘾的可能性，但从未得到证实。 MicroRNA-21（miR-21）是一种独特的miRNA，因为在迄今为止分析的大多数肿瘤类型中它都过表达。尽管人们对miR-21表现出极大的兴趣，但大多数通过miRNA分析和有限的体外功能测定获得了涉及miR-21的数据。为了探索miR-21在体内癌症中的作用，我们使用了Cre和Tet-off技术来产生有条件表达miR-21的小鼠。在这里，我们显示miR-21的过表达导致B前恶性淋巴样表型，表明mir-21是真正的致癌基因。当miR-21失活时，肿瘤在几天内完全消退，部分是由于细胞凋亡。这些结果表明，肿瘤可能会沉迷于oncomiRs并通过miRNAs（例如miR-21）的药理失活来支持治疗人类癌症的努力。

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  • 来源
    《Nature》 |2010年第7311期|P.86-90|共5页
  • 作者

    Pedro P. Medina; Mona Nolde; Frank J. Slack;

  • 作者单位

    Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520, USA;

    rnDepartment of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520, USA Department of Cell Biology, Yale University School of Medicine, PO Box 208002, New Haven, Connecticut 06520, USA;

    rnDepartment of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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