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New papers identify a microRNA that drives both cancer onset and metastasis
Date:7/3/2013

e expression of certain genes as well as other selected microRNAs. Based on these studies, we now know that one miRNA can communicate and repress other miRNAs epigenetically. In this particular case, we have also learned that miR-22 does so by silencing a family of enzymes called TET proteins, which act as tumor suppressors."

In addition, the scientific team, led by first author Su Jung Song, PhD, a postdoctoral fellow in the Pandolfi laboratory, discovered that overexpression of miR-22 also triggers metastasis the spread of cancer from a primary site to other organs, in this case, from breast tissue to the lungs.

Metastasis remains one of the most complex and challenging problems of oncology. Recent studies have demonstrated that as tumors progress, genetic and epigenetic mechanisms may lead to the emergence of a self-renewing metastatic cancer stem cell or cancer-initiating cell, which can enter the blood stream and seed a secondary tumor in a distinct organ.

"We showed that by promoting epithelial to mesenchymal transition [EMT], a process by which cancer cells gain properties that enable them to become both more motile and more invasive, miR-22 promotes aggressive metastatic disease in breast cancer," explains Song, who describes this course of events in the paper published in Cell. Specifically, she adds, miR-22 silences the anti-metastatic miR-200 through direct targeting of TET proteins, as shown in a mouse model.

But, notes Pandolfi, "While these findings are extremely novel, what makes this work even more exciting is its therapeutic implications."

As described in the team's second paper, in Cell Stem Cell, the new findings further identify miR-22 as an epigenetic modifier and key oncogenic determinant for the pathogenesis of myeolodysplastic syndrome (MDS) and leukemia in a mouse model of disease thus identifying a novel therapeutic target for blood and breast malignancies.

"We already h
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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