Research ArticleCancer

Identification of the miR-106b~25 MicroRNA Cluster as a Proto-Oncogenic PTEN-Targeting Intron That Cooperates with Its Host Gene MCM7 in Transformation

Science Signaling  13 Apr 2010:
Vol. 3, Issue 117, pp. ra29
DOI: 10.1126/scisignal.2000594

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A Malignant Combination

The abundance of microRNAs (miRNAs), tiny non–protein-coding RNAs that act as posttranscriptional regulators of gene expression, is frequently altered in cancer; indeed, various miRNAs are thought to act as oncogenes or tumor suppressors. Poliseno et al. investigated the possible role of miRNA regulation of the tumor suppressor PTEN in prostate cancer. They identified miRNAs from several families that targeted the gene encoding PTEN, thereby decreasing PTEN abundance, and showed that the abundance of some of these miRNAs was increased in human prostate cancer. Intriguingly, three PTEN-targeting miRNAs located within an intron of the gene encoding the DNA helicase minichromosome maintenance protein 7 (MCM7), which shows increased abundance in various human cancers, cooperated with MCM7 to transform fibroblasts in vitro and to initiate tumors when overexpressed in the prostates of transgenic mice. Thus, the MCM7 gene locus appears to encode multiple oncogenic elements that cooperate to promote prostate cancer development.

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