Investigating how oncogenic miRNA alters the genetics of Breast Cancer

The underlying causes of breast cancer (BC) are diverse, however, there is a striking association between type 2 diabetes (T2DM) and both the likelihood of a woman developing breast cancer and her risk of dying. While the mechanisms behind this association remain to be fully understood, this project focused on the emerging link between platelet derived microparticles (PMPs) and BC tumourigenesis in the context of a T2DM diagnosis. Other studies have shown that PMPs have the potential to alter target cell function via delivery of RISC-associated miRNAs. Recently, a role for platelet-derived microparticles (PMPs) as drivers of metastasis has emerged for several cancers. This raises the intriguing possibility that an elevated risk of BC development and metastasis in T2DM patients might be explained by increased levels of circulating PMPs. This project has investigated the impact of purified PMPs on a range of BC cell lines and demonstrated that both diabetic platelet derived microparticles (DPMP) and non-diabetic platelet derived microparticles (NDPMP) had different effects, depending on the BC cell type. This project has found, through phenotypic and molecular analysis, including RNA seq, that DPMPs favour influencing triple negative BC, with miR-21 playing an important role in this interaction. NDPMPs, however, still present an influence over other types of BC that should not be ignored, giving them the potential of being used as therapeutic targets as well.