Scientists identify novel inhibitor of huma...(ulate protein synthesis by binding to th...)

Huang notes that one sizeable hurdle in harnessing the power of miRNAs is getting "the right molecule into the right place at the right time" to regulate their function.

"In terms of developing therapeutic agents for cancer, for example, we need to identify small molecules that can get into the bloodstream and get into the cells," he says. "The problem is, to date, no one had been able to show that such miRNA inhibitors exist."

Huang and his colleagues developed a method to identify inhibitors of miRNA pathways in live human cells. The researchers created screening assays, or tests, to look for small molecules or compounds that selectively repress miRNA. They selected miR-21 as the target agent due to its documented role in preventing cell death thereby allowing the unchecked cell proliferation associated with cancer and its elevated levels in various cancers.

The team designed an assay that contained the DNA binding sequence complementary to miR-21, bound to luciferase, the protein fireflies use to create light. Because miRNAs inhibit protein production, when miR-21 is functioning normally, it binds with the complementary sequence and inhibits the translation of luciferase, thus reducing the intensity of the light signal.

"The idea was that when we add small molecules that inhibit the function of miR-21, the light signal will increase," Huang says.

The scientists then screened a "library" of 1,000 compounds and found one molecule that inhibited miR-21 in the assay. The molecule, diazobenzene 2, decreased miR-21 levels by 80 percent and produced a nearly five-fold increase in the intensity of the light signal from the firefly p
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