Intersection from prediction programs is demonstrated to be an important regulator of cancer metastasis

Small RNA filed is still extremely hot. One big question in the field is how to predict one small RNA regulates which gene, or the reverse, one gene is regulated by which small RNA. There are several programs out there (PicTar, TargetScan, miRanda and miRInspector). In this Science paper, the authors used these programs to predict the regulators of their favorite gene EZH2 and found that the intersection miR101 potently regulates EZH2. Doing science, is not only about describing what we discovered, but also about making predictions. Right? What do you think?

Science. 2008 Nov 13. [Epub ahead of print]
Genomic Loss of microRNA-101 Leads to Overexpression of Histone Methyltransferase EZH2 in Cancer.
Varambally S, Cao Q, Mani RS, Shankar S, Wang X, Ateeq B, Laxman B, Cao X, Jing X, Ramnarayanan K, Brenner JC, Yu J, Kim JH, Han B, Tan P, Kumar-Sinha C, Lonigro RJ, Palanisamy N, Maher CA, Chinnaiyan AM.

Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Enhancer of zeste homolog 2 (EZH2) is a mammalian histone methyltransferase that contributes to the epigenetic silencing of target genes and that regulates the survival and metastasis of cancer cells. EZH2 is overexpressed in aggressive solid tumors by mechanisms that remain unclear. Here, we show that the expression and function of EZH2 in cancer cell lines is inhibited by microRNA-101 (miR-101). Analysis of human prostate tumors revealed that miR-101 expression decreases during cancer progression, paralleling an increase in EZH2 expression. One or both of the two genomic loci encoding miR-101 were somatically lost in 37.5% of clinically localized prostate cancers (6/16) and 66.7% of metastatic disease (22/33). We propose that genomic loss of miR-101 in cancer leads to overexpression of EZH2 and concomitant dysregulation of epigenetic pathways, resulting in cancer progression.

PMID: 19008416