MicroRNA Inhibition a Factor in Muscle Cancer Development

Cancer researchers have found that the cells of the childhood muscle-cancer rhabdomyosarcoma lack a specific microRNA activity, and that restoration of this activity stimulates the cells to mature into normal muscle tissue.

Investigators at Ohio State University (Columbus, USA) studied myoblasts (stem cells with the potential to differentiate into muscle), normal muscle cells, and rhabdomyosarcoma cells growing in tissue culture. They were particularly interested in microRNA expression, in light of the recent discovery of the importance of microRNAs in physiological and pathological processes.

Results published in the November 4, 2008, issue of the journal Cancer Cell revealed that cells from human rhabdomyosarcoma tumors showed levels of the microRNA miR-29 that were only 10% or less of those in normal muscle cells. MiR-29 expression was found to be regulated by a protein called NF-kappa B. This protein was detected at high levels in rhabdomyosarcoma cells. NF-kappa B inhibited miR-29 and prevented myoblasts from differentiating into mature muscle cells. Restoration of miR-29 in rhabdomyosarcoma cells that were implanted into mice slowed tumor growth and stimulated cellular differentiation.

"This study shows that there is a connection between this microRNA, muscle development, and rhabdomyosarcoma,” said senior author Dr. Denis C. Guttridge, associate professor of molecular virology, immunology, and medical genetics at Ohio State University. "The findings should give us a better understanding of muscle repair and development, and of rhabdomyosarcoma, and could lead to new treatments for this and other muscle diseases. High levels of the NF-kappa B protein inhibit miR-29 activity, which blocks differentiation and causes muscle cells to remain immature. If we can restore the levels of miR-29 in patients it might provide a new therapy for this childhood cancer and perhaps other muscle diseases.”

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