Researchers have identified a novel mechanism that stimulates the death of malignant pleural mesothelioma (MPM) cells, providing potential therapeutic targets for the treatment of this aggressive disease.
The study, “MicroRNA-302b Targets Mcl-1 And Inhibits Cell Proliferation And Induces Apoptosis In Malignant Pleural Mesothelioma Cells,” was conducted by a research team from the University of Florida and published in the American Journal of Cancer Research.
Human DNA contains information for the production of proteins necessary for cell function stored in the genes, but it also includes information for molecules that regulate protein synthesis, such as microRNAs.
MicroRNAs, or simply miRs, are able to bind to an mRNA molecule (a copy of the coding information for the production of the corresponding protein) and interfere with the production of that protein. One miR can bind to many different mRNA molecules, which makes miRs powerful regulators of gene expression.
In recent years, miRs have been the subject of increasing attention in cancer, as these molecules can regulate the production of proteins that contribute to either cancer cell survival or death.
One such protein is Mcl-1. In both healthy and cancer cells, Mcl-1 contributes to cell survival. Another protein that has been associated with the progression of a variety of tumor types, including MPM, is the ephrin A2 (EphA2) receptor. In a previous study, researchers demonstrated that activation of this receptor by ephrin-A1, a molecule involved in several cellular functions, led to marked regression of MPM tumor cells.
Now, the team found that ephrin-A1 exerts its beneficial effect by stimulating the production of miR-302b in MPM cells. The increased production of this molecule then causes a decrease in the levels of the pro-survival protein Mcl-1, impairing its protective activity in MPM cells. This, in turn, inhibits MPM cell proliferation and growth, resulting in a significant increase in cell death.
“For the present study, we identified a novel mechanism of ephrin-A1-mediated tumor growth inhibition in [MPM],” the researchers wrote. “We demonstrate that ephrin-A1 treatment leads to miR-302b expression in MPM cells. In addition, miR-302b functionally targets the pro-survival molecule, Mcl-1, which results in its repression and induces [death] in [MPM cells].”
“Together these findings suggest that ephrin-A1 may have a distinct role in controlling tumor growth pathways and may be a promising candidate in the development of novel therapeutic strategies against [MPM],” the authors wrote.