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Perspectives

Diverse Ways to Control p27Kip1 Function: miRNAs Come into Play

Carlos le Sage, Remco Nagel and Reuven Agami

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microRNAs (miRNAs) are small RNA molecules controlling messenger RNA (mRNA) and protein abundance. Since their discovery, research has been aimed at identifying the functions and target genes of miRNAs. A number of computer algorithms have been developed capable of predicting putative targets for any given miRNA. However, they might predict many false-positive targets and on top of that some true targets could be missed. This reflects the incomplete knowledge we still have concerning the rules governing true and effective miRNA-mRNA interactions. To experimentally identify miRNA-target genes, we have recently developed a genetic approach and employed it on p27Kip1, a hapo-insufficient tumor suppressor and cell cycle inhibitor. Here we review the difficulties interpreting the data from available computer algorithms, and critically address the pros and cons of our genetic screening method. Additionally, we focus on the different ways in which p27 is managed, argue how miRNAs could be involved in the regulation of p27 in both normal and malignant conditions, and discuss possible use of this knowledge for cancer therapy.

Authors

Carlos le Sage

The Netherlands Cancer Institute; Amsterdam, The Netherlands

Remco Nagel

The Netherlands Cancer Institute; Amsterdam, The Netherlands

Reuven Agami

The Netherlands Cancer Institute; Amsterdam, The Netherlands

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If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.