Extracellular vesicle encapsulated microRNAs and breast cancer

O'Neill, Clodagh
Breast cancer is the most prevalent cancer among women worldwide. There is a clear need for earlier detection methods and more personalised treatments. Extracellular vesicle encapsulated microRNA (EV-miR) provide novel potential in this endeavour. Identifying an EV-miR breast cancer specific signature has the power to detect cancer early, differentiate between subtypes as well as predict the tumours response to therapy and overall survival. This study uncovered a number of miRNAs that were selectively enriched in cancer cell derived EVs including miR-184, miR-1 and miR-1246. While in serum EVs, selective enrichment of miR-451a, miR-184 and miR-122-5p was identified. If the right standardisation and reporting is up held, EV-miRNAs are excellent candidates for use as diagnostic and prognostic biomarkers in breast cancer. EVs are versatile nanocarriers that can be engineered to contain to deliver a tumour suppressor miRNA signature that can then be delivered to the cancer site. EV–miRNAs have the power to revolutionise the treatment of cancer but there are areas that remain poorly understood including EVs interactions in vivo. This study presents a novel method of labelling EVs using the PE specific ligand duramycin. The novel pre-clinical labelling and imaging method described is significant to the EV field and the data can inform extrapolation to other models. The strength of the tumour suppressor signature loaded into EVs is integral to the success of the EV-miRNA cancer treatment. MiRNAs are a tiny cog in a well-oiled regulatory machine and identifying and utilising multiple members in a gene cluster could provide the necessary therapeutic strength required to treat cancer. The data presented in this thesis suggests combining miR-379 and miR-758 from the same gene cluster will have strong anti cancer synergy through shared regulation of pathways involved in cell remodelling and angiogenesis. Furthermore, engineering EVs to contain miRNA 379 and miR-758 has strong potential to treat breast cancer.
NUI Galway
Publisher DOI
Attribution-NonCommercial-NoDerivs 3.0 Ireland