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Versatile microRNAs choke off cancer blood supply, suppress metastasis
Date:9/11/2013

type

Sood and colleagues analyzed hundreds of annotated ovarian, renal, breast and non-small cell lung cancer samples from The Cancer Genome Atlas for expression of all five miR-200 family members. Low expression of miR-200 was associated with poor survival in lung, ovarian and renal cancers, but improved survival for breast cancer.

However, they found a striking difference when they analyzed breast cancers by those that are hormone-receptor positive (luminal) and those that lack hormone receptors or the HER2 protein, called triple-negative breast cancer. High expression for miR-200 was associated with improved survival for triple-negative disease, which is more difficult to treat due to its lack of therapeutic targets.

Gene expression analysis of ovarian and lung cancer cell lines pointed to an angiogenesis network involving both IL-8 and CXCL1. By mining public miRNA and messenger RNA databases, the researchers found:

  • An inverse relationship between expression of four of the five members of the miR-200 family and IL-8.

  • Lung, ovarian, kidney and triple-negative breast cancer all have elevated IL-8 and CXCL1 expression compared to hormone-positive breast cancers.

  • Elevated IL-8 associated with poor overall survival in lung, ovarian, renal and triple-negative breast cancer cases.

    Treating cancer cell lines with miR-200 decreased levels of IL-8 and CXCL1, and the team also identified binding sites for these genes, meaning they are direct miR-200 targets.

Mice treated with miR-200 family members delivered in a fatty nanoparticle developed by Sood and Gabriel Lopez, M.D., professor of Experimental Therapeutics, had steep reductions in lung cancer tumor volume, tumor size and the density of small blood vessels compared to controls. Results were repeated with kidney, ovarian and triple-negative breast cancers.

miR-200 nanoparticles stymie metastasis

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Contact: Scott Merville
smerville@mdanderson.org
713-516-4855
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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