Rewire Act

Cancer cells show rewired, fragmented microRNA networks

Carlo CroceA multicenter study led by scientists at the OSUCCC – James shows that microRNA (miRNA) molecules work together in single, well-connected networks to control functions in healthy cells, but in cancer cells the networks are rewired an fragmented.

The research introduces a way of discovering cancer genes, identifies new miRNAs that can be used as targets for drug development, and pinpoints possible cancer-related proteins, says study lead Carlo Croce, MD, professor of Molecular Virology, Immunology and Medical Genetics, and John W. Wolfe Chair in Human Cancer Genetics.

MiRNAs are noncoding RNAs that control cell functions such as growth, proliferation and differentiation. Abnormal miRNA expression plays an important role in cancer development. This study found that miRNAs in healthy cells interact in a network that, when mapped, resembles a family tree with dozens to hundreds of members. Each cell type has its own network, with particular miRNAs serving as central hubs within the network.

In cancer cells, the single network is replaced by subnetworks that usually include small detached clusters of two to six miRNAs. “These small groups that exist outside the main network were unexpected,” Croce says. “Some of these miRNA outliers are well-known cancer genes, but the involvement of others in cancer was unknown.”

The study suggests that key cancer genes can be identified on the basis of their relationship to other genes, as well as on their overexpression or loss.

Published in the journal Genome Research.

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