microRNA Expression Regulates Tumor Growth in Mouse Lung Cancer Model

Levels of a specific microRNA, miR-21, have been found to regulate the progression of non-small-cell lung cancer (NSCLC) in a mouse model.

To study the in vivo roll of miR-21 in NSCLC investigators at the University of Texas Southwestern Medical Center (Dallas, USA) genetically engineered two distinct lines of mice, one that overexpressed miR-21 and one that did not express this microRNA at all.

They reported in the September 14, 2010, issue of the journal Cancer Cell that overexpression of miR-21 enhanced tumorigenesis, and that genetic deletion of miR-21 partially protected against tumor formation. At 18 weeks of age, mice with overexpressed miR-21 had significantly more tumors than NSCLC animals with normal levels of miR-21. On the other hand, overexpression of miR-21 by itself did not induce cancer formation in otherwise healthy animals.

The investigators determined that at the molecular level miR-21 promoted tumorigenesis by inhibiting tumor suppressors of the Ras/MEK/ERK pathway, which in turn inhibited apoptosis and allowed the cancer cells to grow. Cancer cells growing in mice with no miR-21 expression were more susceptible to certain kinds of chemotherapy, suggesting that inhibiting miR-21 in lung-cancer patients could be of therapeutic value.

"Methods currently exist to pharmacologically manipulate molecules like miR-21,” said senior author Dr. Eric Olson, professor of molecular biology at the University of Texas Southwestern Medical Center. "More research will be needed before we know whether this is applicable to humans, but it's possible that a drug designed to inhibit miR-21 could help keep cancer at bay.”

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University of Texas Southwestern Medical Center