Researchers from the Nuffield Department of Surgical Sciences, Nuffield Department of Medicine and Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, have been investigating microRNA sequences and their influence on the migration and wider metastasis of prostate cancer cells around the body.
Prostate cancer is the second most fatal cancer in males, due in part to its slow growth and difficulties in early diagnosis before it spreads. Once spread, standard treatments are less effective and the disease is often incurable. Understanding mechanisms that modulate and cause the process of cancer metastasis is important in order for us to better understand how to detect, prevent and treat it.
Led by Claire Edwards, postdoctoral researcher Srinivasa Rao Rao devised a series of transcriptomic and functional screening strategies. This novel combination of migrational and morphological analysis allowed the team to focus on the wider biological relevance of microRNA in the development of prostate cancer.
After studying the entire microRNA genome, the team focused on overexpressing microRNAs belonging to specific families, specifically, those known as miR-372 and miR-302 clusters, which emerged as interesting candidates in the regulation of prostate cancer. 16% of microRNAs screened in this novel method, were found to decrease the rate of cell migration when dysregulated. Similarly, 19% of microRNAs were found to alter the morphology and shape of cancer cells.
This publication demonstrates an application using a series of integrated screening approaches to enhance the specificity and accuracy of screens. By using a variety of screening strategies in succession, the team were able to narrow down the microRNA candidates to those more likely to be directly involved in prostate cancer progression. There are additional applications of this work through the use of these relatively stable microRNAs as diagnostics markers for the earlier detection and diagnosis of prostate cancer.
Claire Edwards, Associate Professor at the Nuffield Department of Surgical Sciences, says;
“Through our collaboration with Daniel Ebner, we have been able to develop a screen to rapidly discover those microRNAs that could reduce migration and so deduce which of them may play a role in prostate cancer metastasis.”
To read the publication in full, see here.
Claire Edwards is an Associate Professor of Bone Oncology. Her main focuses are on obesity and adipokines in cancer-induced bone disease, metabolism and miRNA in prostate cancer bone metastases and bone marrow stromal cells in the pathogenesis of cancer-induced bone disease.
Daniel Ebner is a Principle investigator at the Nuffield Department of Medicine. He worked with the Target Discovery Institute to develop new target screening methodologies, investigate disease pathways as a means for identifying ‘drug targets’ and advance therapeutically relevant targets for drug development.
Freddie Hamdy is a Nuffield Professor of Surgery with a research focus on management of urological malignancies, in particular prostate and bladder cancer He is the Chief Investigator of many studies including the ProtecT (Prostate testing for cancer and Treatment) study of case-finding and randomised controlled trial of treatment effectiveness in prostate cancer – the largest of its kind worldwide.
This work was supported by the FP7 Marie Curie Initial Training Network PRO-NEST, Cancer Research UK, through the Cancer Research UK Oxford Centre Development Fund and through the University of Oxford Medical Research Fund.