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

• Published in: Nature (London) 2010-09, Vol.467 (7311), p.86-90
• Main Authors: Medina, Pedro P., Nolde, Mona, Slack, Frank J.
• Format: Article
• Language: English
• Subjects: 631/208/200; 631/337/384/331; 631/80/82/23; 692/699/67/1990/291/1621/1915; Addictions; Animal tumors. Experimental tumors; Animals; Apoptosis; Biological and medical sciences; Blood; Bone marrow; Cancer; Cancer therapies; Carcinogenesis; Experimental malignant blood diseases; Gene expression; Health aspects; Humanities and Social Sciences; Inactivation; letter; Lymphoma; Lymphoma, B-Cell - metabolism; Lymphomas; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; multidisciplinary; Oncogenes; Pathology; Precursor Cells, B-Lymphoid - metabolism; Science; Science (multidisciplinary); Siblings; Spleen; Tumors
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature09284

Tumour addicted to oncomiR MicroRNAs (miRNAs) — small RNA molecules that regulate gene expression and have an important role in establishing cell identity — have been linked to human cancers, where they are referred to as oncomiRs. One model of cancer development proposes that proliferating cells become 'addicted' to activating mutations in an oncogene, and it has been suggested that tumours may also become dependent on oncomiRs. Work in mice that were engineered to conditionally express microRNA-21 (miR-21), which is overexpressed in most tumour types so far analysed, now shows that miR-21 induces pre-B-cell lymphoma. In the absence of miR-21, malignant cells undergo apoptosis and regress, as would be expected if they were addicted to its presence. The pharmacological inactivation of 'oncomiR-21' and other similar miRNAs may therefore be of therapeutic benefit. One model for cancer development posits that the proliferating cells in a tumour can become 'addicted' to activating mutations in an oncogene. With the realization that certain microRNAs promote tumorigenesis, it has been proposed that tumours may also become dependent on such 'oncomiRs'. Here, evidence is provided that the gene encoding microRNA-21 is an oncogene, and that in its absence, tumours undergo apoptosis and regress. Thus tumours can indeed become addicted to oncomiRs. 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 1 . 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 2 , 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 3 , 4 , and the possibility of oncomiR addiction has been proposed but never demonstrated 3 . 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 dat