生物谷Bioon.com 訊 miRNA是調控基因表達、在確定細胞身份中起重要作用的小RNA分子,，它們被與人類癌癥聯(lián)系了起來,，在人類癌癥中，它們被稱為“oncomiRs”,。關于癌癥形成的一個模型認為,，增值的細胞變得對激發(fā)某個致癌基因中的突變“上癮”，而且也曾有人提出,，腫瘤也會變得依賴于“oncomiRs”,。
現(xiàn)在，用小鼠（研究人員通過基因工程方法使這些小鼠表達微RNA-21 (miR-21),，該微RNA迄今為止在所分析過的大多數(shù)腫瘤類型中都過度表達）所做研究表明,，miR-21誘導pre-B-cell淋巴瘤；在沒有它的情況下,，惡性細胞發(fā)生凋亡和退化,，正如按它們對其存在“上癮”（的假設）所預期的那樣。因此,，“oncomiR-21”和其他類似 miRNA的藥理滅活應有治療效果,。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
