Extracellular vesicle encapsulated microRNAs and breast cancer
Date
2023-02-24Embargo Date
2025-02-20
Author
O'Neill, Clodagh
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Abstract
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.