Tracing the Pathway to Cancer Suppression by a MicroRNA Mediator

MicroRNAs play an essential role in development and are mediators of a variety of diseases, including cancer. In a study published this week in Proceedings of the National Academy of Sciences researchers highlight the role of the mda-7/IL-24 gene in influencing microRNAs. mda-7/IL-24 has been known for decades to play a role in suppressing a majority of cancer types and thus these findings could have exciting implications for development of cancer treatments.

The research was led by Paul B. Fisher, Ph.D. from Virginia Commonwealth University, who originally discovered the mda-7/IL-24 gene and has since published a number of papers, in collaboration with his colleagues, detailing how the gene can suppress cancer by directly influencing two important mediators of apoptosis and toxic autophagy. They have also been working on mda-7/IL-24 viral gene therapies, purified protein treatments, and T-cell-delivered therapies.

In the current study, the researchers showed that mda-7/IL-24 reduces the expression of the miRNA-processing enzyme, DICER, in cancer cells only. In cell line and mouse model experiments, overexpression of DICER was shown to rescue cancer cells from mda-7/IL-24 mediate cell death.

Another key mediator in this process was found to be microphthalmia-associated transcription factor (MITF), which regulates cellular response to reactive oxygen species (ROS). The scientists showed that mda-7/IL-24 down-regulates MITF, which leads to down-regulation of DICER.

"This is an exciting and previously unknown link between mda-7/IL-24 and ROS/MITF/DICER that we plan to continue exploring," said Fisher. "This research may open up new therapeutic targets, and monitoring the levels of these components could provide important biomarkers to help inform the effectiveness of mda-7/IL-24-based therapies."