Editors' ChoiceCancer

A New “Fix” for Cancer

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Science Translational Medicine  15 Sep 2010:
Vol. 2, Issue 49, pp. 49ec142
DOI: 10.1126/scitranslmed.3001679

Despite the complexity of cancer, it is clear that certain tumors can become wholly dependent on single genes for their development and survival, a phenomenon the late Bernard Weinstein termed “oncogene addiction.” In recent years, it has also become clear that genes and their coding RNAs are not the only determinants of diseases such as cancer. Indeed, several microRNAs (miRNAs), a class of small noncoding RNA molecules that regulate gene expression at the posttranscriptional level, are up-regulated in cancer versus normal tissues and may be molecular markers of disease. However, no one had conclusively demonstrated that a miRNA was oncogenic in vivo or that cancers could become addicted to a miRNA. New work by Medina et al. shows that miRNA-21 is indeed a bona fide oncomiR (or oncogenic miRNA) that is critical for the development and progression of pre–B cell lymphoma.

The authors created a transgenic mouse model with a Tet-Off system, in which doxycycline could be used to turn off expression of miRNA-21. Sustained miRNA-21 overexpression led to pre–B cell lymphomas in these mice and clinical features that recapitulated human lymphoma. However, supplementation of doxycycline in the diets of mice with established, miRNA-21–driven lymphomas led to tumor regression and improved survival as compared with that of mice fed standard diets in which expression of miRNA-21 remained on. miRNA-21 appears to have a role in preventing apoptosis because doxycycline-fed mice had increased apoptosis in their tumors.

These results are intriguing, and they show direct evidence that miRNA-21 is an oncomiR, to which pre–B cell lymphomas can become addicted. That interference with miRNA-21 expression in this mouse model led to regression of these lymphomas and that miRNA-21 is commonly overexpressed in many cancers highlight that miRNA-21 is a driver rather than a mere marker of cancer. Given these results, inhibitors of miRNA-21 function—possibly small interfering RNA–based—should be developed to cut off this new “fix” for cancer cells.

P. P. Medina et al., OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 467, 86–90 (2010). [Abstract]

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