Researchers at Columbia University Medical Center (CUMC) and other institutions have uncovered a vast new gene regulatory network in mammalian cells that could explain genetic variability in cancer and other diseases. Four studies bearing on this new regulatory network appear in the October 14, 2011 issue of Cell. "The discovery of this regulatory network fills in a missing piece in the puzzle of cell regulation and allows us to identify genes never before associated with a particular type of tumor or disease," said Dr. Andrea Califano, professor of systems biology, director of the Columbia Initiative in Systems Biology, and senior author of the CUMC research team’s article. For decades, scientists have thought that the primary role of messenger RNA (mRNA) is to shuttle information from the DNA to the ribosomes, the sites of protein synthesis. However, these new studies suggest that the mRNA of one gene can control, and be controlled by, the mRNA of other genes via a large pool of microRNA molecules, with dozens to hundreds of genes working together in complex self-regulating sub-networks. The findings have the potential to broaden investigations into how tumors develop and grow, who is at risk for cancer, and how to identify and inactivate key molecules that encourage the growth and spread of cancer. For example, in the case of the phosphatase and tensin homolog gene (PTEN), a major tumor suppressor, deletions of its mRNA network regulators in patients appear to be as damaging as mutations of the gene itself in several types of cancer, the studies show. The newly identified regulatory network (called the mPR network by the CUMC investigators) allows mRNAs to communicate through small bits of RNA called microRNAs.
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