Zorica Nakevska

Supervisor: Yangxin Fu

Project: A new potential treatment in advanced ovarian cancer

"Chemical changes to RNA have significant impacts on the fate of a cell, and determining their downstream effects is crucial for understanding how cancer cells survive."

Discovering the partners of the tumour-promoting NSUN2 in ovarian cancer

Epithelial ovarian cancer (EOC) is one of the leading causes of death related to gynecologic cancers. Current treatments against advanced EOC are ineffective, highlighting an urgent need for novel treatments. 

Research in the Fu Lab has determined that an enzyme called NSUN2, which modifies RNA molecules in the cell, has a tumour-promoting role in EOC and is correlated with reduced survival in ovarian cancer patients when it is present at high levels. We have found that while reducing NSUN2 levels slows the growth of EOC cells, the cells have adaptive mechanisms to overcome this effect over time. We suspect that the adaptive mechanism involves other genes that step in to help when there is not enough NSUN2. 

To determine the partner genes, we used a computer analysis to find potential suspects. Of the potential partners that came up, the strongest result led to a protein called NHP2. We hypothesize that simultaneous deactivation of NSUN2 and NHP2 could have even greater effects on cancer cell growth than just NSUN2 alone. To test this, we will analyze how well EOC cells grow when NSUN2 and NHP2 are deactivated compared to when NSUN2 alone is deactivated. 

The experiments we will use to accomplish this are different assays that test the speed of cell growth, how well cells can survive, and how often cells are dying. If we obtain the expected results, we will take it one step further and test our hypothesis using animal models to analyze the rate of tumour growth. If we do not obtain the expected results of NHP2 being the partner of NSUN2, we will use the same strategies to test the other genes that came up as potential partners. 

Success in our research findings could redefine ovarian cancer treatment strategies and provide a potential treatment option for patients with advanced EOC, which are currently limited.

Zorica Nakevska was supervised by Yangxin Fu and her summer studentship was funded by the Alberta Women’s Health Foundation. She is enrolled in the Bachelor of Science in Honors Molecular, Cellular and Developmental Biology program.