Breast cancer is the leading cause of cancer deaths among women worldwide. Breast cancer spread to distant sites is the main contributor of these fatalities. The first step in this process is often spread to adjacent lymph nodes. Indeed, lymph node metastasis is a strong indicator of patient prognosis, the mechanisms involved have not yet been elucidated. Understanding this process could aid identification of methods to prevent this pivotal step in breast cancer progression. It is thought that factors secreted by the tumour aid the spread to the lymph nodes. Both Vascular endothelial growth factor(VEGF)-C and cyclooxygenase(COX)-2 have previously been shown to play a role in lymph node metastasis in various cancers. Recent unpublished work from this laboratory has shown elevated VEGF-C levels in serum of breast cancer patients compared to healthy controls. MicroRNAs are short non-coding strands of RNA that regulate gene expression. Previous work analysing microRNA-379(miR-379) found reduced expression in breast tumour tissue compared to healthy controls. RNA sequencing analysis of cells engineered to over-express miR-379, identified prostaglandin E synthase(PTGES) as a novel target. This gene is induced by pro-inflammatory cytokines and has been shown to be elevated in breast tumours. Further computational analysis also revealed a novel miRNA(miR-3148), with common binding sites on key lymphangiogenic mediators(VEGF-C, VEGF-D and COX-2). Therefore, the aim of this project is to determine the expression of miR-379 and miR-3148 in patient serums and tumour tissues and correlate with previously established VEGF-C and VEGF-D levels and identify any relationship with patient clinicopathological details.
