Funding outcome

Around 3,900 women are diagnosed with ovarian cancer and 1,900 women die of the disease each year in Canada, making it the leading cause of death related to gynecologic cancers. Most epithelial ovarian cancer (EOC) patients are diagnosed at late stages and there are currently no effective treatments for advanced EOC, so it is crucial to develop new treatment strategies. Research in Dr. Fu's lab has been focused on the role of an enzyme called NSUN2 in EOC. NSUN2 modifies RNA molecules and thereby regulates their expression and functions in the cell. We have found that knockdown of NSUN2 (decreased expression of NSUN2) leads to decreased cell growth and survival and alters the mRNA levels of hundreds of genes in EOC cells, indicating that NSUN2 plays a pro-tumorigenic role in EOC. However, the molecular mechanisms underlying the pro-tumorigenic functions of NSUN2 remain to be determined. We hypothesize that the pro-tumorigenic functions of NSUN2 depend on its enzyme activity of modifying RNAs. To test this hypothesis, we will express normal NSUN2 and the enzyme-dead NSUN2 mutants, which have lost the ability to modify RNAs, in EOC cells and compare their effect on cell growth and survival. We will use a variety of cellular and molecular techniques, and methods to measure different aspects of NSUN2 effects on cell behaviors. We expect that normal NSUN2, but not the enzyme-dead NSUN2 mutants, will increase cell growth and survival in EOC cells. Results from this project will determine whether inactivation of the enzyme activity of NSUN2 will abolish its pro-tumorigenic function and whether inhibiting the enzyme activity of NSUN2 could be a potential therapeutic strategy to treat EOC. The ultimate goal of our research is to develop novel and more effective treatments for EOC to improve the survival and quality of life of EOC patients.