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Replacing absent microRNAs could make tumors less invasive, more treatable
Date:3/31/2008

umors.

"The importance of this finding is, first, that miR-200 may represent a good marker to stage cancer," Peter said, and "second, that reintroducing miR-200 into late cancer cells could provide a new form of treatment, preventing these cells from going through EMT and becoming more invasive."

Physicians already have a set of fairly reliable markers for carcinoma. Tumors with high levels of E-cadherin tend to be tightly tethered to nearby cells and less likely to break free and travel to other sites. Those with high Vimentin levels represent mesenchymal cells able to pass though other tissues.

Peter and colleagues found that miR-200 added mechanistic depth to those markers. Every tumor cell line the researchers tested that had the epithelial marker E-cadherin and not the mesenchymal marker Vimentin, had high amounts of miR-200. Every cell line with high Vimentin and no E-cadherin had no detectable miR-200.

"So we were able to show a complete correlation between miR-200 and E-cadherin/Vimentin expression," Peter added.

The authors found that miR-200 microRNAs helped regulate EMT transition. They bind directly to non-coding regions in the RNA of ZEB1 and ZEB2, known blockers of E-cadherin transcription. Both ZEB proteins have previously been implicated in human malignancies, ZEB1 in aggressive colorectal and uterine cancers, and ZEB2 in advanced stages of ovarian, gastric and pancreatic tumors.

By inhibiting miR-200, Peter and his coworkers could induce EMT. More important, by introducing miR-200, they managed to activate production of E-cadherin protein and reverse tumors from a more-invasive mesenchymal into a less-invasive epithelial form.

"In a previous paper we found that another micro RNA, let-7, drives tumor progression at an earlier stage," Peter said. "Let-7 appears to be a key player in preventing a cancer from becoming more aggressive. Now we want to figure out how these two micro RNAs work
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Contact: John Easton
john.easton@uchospitals.edu
773-702-6241
University of Chicago Medical Center
Source:Eurekalert

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