The Kidney Foundation of Canada

Dre Sandra Turcotte

Dre Sandra Turcotte

Université de Moncton, NB

Studying the interaction between miR-2355 and the Sushi-domain-containing protein 4 to investigate a role for the complement system in VHL-inactivated renal cell carcinoma

2018-2020:  $100,000 |  Biomedical Research Grants  |  Category: Cancer

Lay Summary

There are 6,600 adults in Canada that will be diagnosed with kidney cancer in 2017 and about 2,000 will die from this disease. It is one of the ten most common types of cancer diagnosed worldwide. Renal Cell Carcinoma (RCC) incidence increases with age (median age is 64 years) and is higher in men than women by a 2:1 ratio. In addition to obesity, hypertension and smoking, medical conditions such as chronic kidney disease, haemodialysis and kidney transplantation are risk factors associated with RCC. Importantly, intratumor heterogeneity showed variability in mutational signatures across the tumor. Furthermore, these tumors are highly vascular at the metastatic stage and no molecular markers or curative treatments are available. Thus, a better understanding of kidney carcinogenesis is crucial to develop new approaches to detect and treat this disease.

Alterations (mutations) that inactivate the von Hippel-Lindau (VHL) tumor suppressor gene are an important discovery reported in up to 85% of RCC cases. Our lab investigates the molecular functions of the VHL tumor suppressor gene using genomics to metabolomics approaches to further improve our knowledge of VHL-inactivated tumors. This research program focuses on microRNAs (miRNAs), which are negative regulators of gene expression. Dysregulation of miRNAs have been implicated in several diseases, including kidney cancer. We previously identified a signature profile of 32 VHL-regulated miRNAs in cells and in a cohort of patients with mutations in the VHL gene. From this, we found an overexpression of miR-2355 associated with a negative regulation of the Sushi Domain-Containing Protein 4 (SUSD4). Here, our work aims to characterize the interaction between miR-2355 and SUSD4 to demonstrate their functional role in clear cell RCC carcinogenesis. Outcomes from this study will provide new insights into VHL-inactivated tumors that could lead to the development of therapeutic targets for kidney cancer.