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Yale Scientists Find MicroRNA Regulates Ras Cancer Gene

Research in the laboratory of Assistant Professor Frank J. Slack at Yale University has identified a new way that a familiar gene is regulated in lung cancer, presenting new possibilities for diagnosis and treatment. The work is reported in March issues of the journals Cell and Developmental Cell.

The oncogene Ras is out of control in about 20 percent of cancers where it is over-expressed or activated by mutation. According to Slack, a member of the Yale Cancer Center, it is one of the most identifiable causes in some forms of lung cancer. His team has identified let-7, a natural and separately transcribed RNA that maps to a chromosomal region associated with lung cancer as a regulator of Ras expression.

DNA of plants and animals contains sequences encoding microRNAs, important regulators of development, that control processes determining cell type and cell death.

"The let-7 microRNA regulates Ras by binding to the message for Ras and likely inhibits translation of the Ras protein," said Slack. "The microRNA does not revert a mutated Ras to normal; instead it acts like a brake on an accelerated Ras."

Lung cancer currently has a poor prognosis with less than 15 percent of patients surviving five years. The lungs, however, are relatively accessible for inhalation of potential gene therapy agents. "While this is not likely to cure the cancer," said Slack, "after diagnosis, gene therapy with let-7 may be a way to alleviate or slow it down."

This work arose from Slack's basic research in the department of molecular, cellular and developmental biology on the nematode round worms, C. elegans. He found that these worms require let-7 RNA for normal development to occur. Without it, cells do not stop dividing and fail to differentiate into the normal structures of the worm ?instead they make an excess of their cells.

After identifying let-7 as a cell division regulator, Slack's team used bioinformatics and found the relationship
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Source:Yale University


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