Scientists find lung cancer clues in worms

Scientists have searched from the depths of the rainforests to the minute intricacies of the cell in their quest for cancer treatments, but a team at Yale has found promise in a lowly worm.

University researchers have found a family of microRNAs which regulate Ras, a known cancer gene. The finding, published in the March 11 issue of Cell, presents possible lung cancer treatments. Biology professor Frank Slack, the study’s senior author, said Ras is commonly over-expressed in lung and pancreatic cancers.

“An increase in function of the protein encoded by Ras contributes to the malignant nature of the cancer cell,” said Dr. Jose Costa, a pathology professor and deputy director of the Yale Cancer Center. “There is no question that [Ras] plays a role in some types of lung cancer and even the lesions that precede lung cancer.”

The study found the let-7 micro-RNA family regulates the production of Ras protein by examining the micro-RNA family’s function in a type of worm. This specific micro-RNA family regulates a gene similar to Ras in the worm. Since 60 percent of the genes found in the studied worm are also present in humans, Slack said the same mechanism might be observed in people.

Through a collaboration with researchers at Ambion, a biotech company in Texas, Johnson said the scientists showed Ras is regulated by the same mechanism in human and worm cells.

The let-7 family’s microRNA presumably inhibit Ras protein formation by binding to the protein’s precursor, Slack said.

Slack said lung cancer patients have low amounts of let-7, which result in a high degree of Ras expression.

The discovery of a Ras regulation mechanism presents potential treatment options.

“Perhaps we can give these patients back this microRNA. It is potentially feasible to think about giving patients back some of this microRNA through an aerosol or a virus,” Slack said.

Steve Johnson GRD ’01 ’04, the paper’s lead author and a post-doctoral fellow at the Stanford University School of Medicine, said future treatments could be aimed at down-regulating the Ras gene, decreasing its expression to normal levels.

Both mutations and a change in the micro-RNA regulator can cause an overexpression of the Ras gene.

“The main implications are that this could be used to possibly detect certain types of lung cancer where they haven’t found a mutated form of Ras, but Ras is still up regulated,” Johnson said.


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