Pair of microRNA molecules controls major oncogene in most common leukemia

Researchers at Ohio State have been leaders in characterizing the role of miRNAs in cancer development. These small molecules are single-stranded RNA molecules that can act either as tumor suppressors or oncogenes. They can block transcription of genes by stopping them from producing messenger RNA or can inhibit translation of the genes by blocking production of proteins from messenger RNA, according to Pekarsky. Earlier this year the investigators provided the first direct evidence that over-expression of an miRNA molecule could result in development of cancer have since identified a number of miRNAs associated with B-cell chronic lymphocytic leukemia that appear to promote tumor development. But the protective miR-29 and miR-181 molecules are emerging as the most important miRNAs discovered to date, Pekarsky said. "MicroRNAs such as these could prove to be as powerful as the protein transcription factors that we know can turn genes on and off," he said.

The researchers studied TCL1 expression and miRNA expression in 23 samples of indolent B-CLL, 25 samples of aggressive B-CLL, and 32 samples of B-CLL exhibiting a chromosomal deletion, which makes it the most difficult type to treat. They found that TCL1 over-expression correlated with the two most aggressive forms of the cancer. To determine which miRNAs targeted TCL1, they used microRNA-microchips and elaborate computer programs to identify miR-29 and miR-181.

Regulation of TCL1 expression by these two miRNAs is relevant to all the three groups of cells studied, Pekarsky said. "You can look at the miRNA profile and say whether the cancer is aggressive or indolent," he said. And of the two miRNAs, miR-29 offers the most predictive power, Pekarsky added.