Canine microRNA targets in cancer

Advisor: Geoffrey Wood, Pathobiology

microRNAs are small non-coding RNA that inhibit translation of mRNAs into protein, based on sequence complementarity with target mRNA. Each microRNA has multiple target genes and can inhibit activity of multiple cellular signaling pathways. Changes in expression of specific microRNAs are known to lead to changes in expression of genes involved in cancer, and these microRNA can act not only within the tumour, but also in distant tissues as they are released into blood. We have previously demonstrated that blood levels of specific microRNA are altered in dogs with osteosarcoma (bone cancer) and lymphoma (lymph node cancer) compared to normal dogs, and that these changes in microRNA levels correlate with treatment outcome. These microRNA may serve as non-invasive biomarkers for cancer prognosis, but the underlying biological meaning of the changes in microRNA are not understood, and the microRNA expressed in the tumour itself does not always match those that change in blood.
This project will use already generated datasets to explore: 1) what signaling pathways are affected by the changes in microRNA levels, and 2) whether combinations of multiple microRNA changes can predict disease outcome better than levels of single microRNAs. We have matched microRNA levels and tumour RNA-seq data from the same lymphoma patients, so confirmation of pathway regulation can be tested. The objectives are to gain a better understanding of the underlying biology of microRNAs in cancer and to design a better predictive test for cancer outcome based on changes in multiple microRNA levels in blood. Because of the very high homology of canine and human microRNA, it is anticipated that the findings will apply to both human and canine cancer.