Poster Presentation Australasian Extracellular Vesicles Conference 2018

Circulating exosomal miRNAs regulate epithelial ovarian cancer progression (#84)

Shayna Sharma 1 , Andrew Lai 1 , Dominic Guanzon 1 , Terry Morgan 2 , Lewis C Perrin 3 4 , John D Hooper 3 4 5 , Carlos Salomon 1 6
  1. Faculty of Medicine, University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia
  2. Department of Pathology and Obstetrics, Oregon Health & Science University, Portland, Oregon, USA
  3. Mater Health Services, Mater Adult Hospital, Brisbane, Queensland, Australia
  4. Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia
  5. Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, Brisbane, Queensland, Australia
  6. Department of Clinical Biochemistry and Immunology, University of Concenpcion, Concenpcion, Chile

Introduction: Exosomes have shown promise as early biomarkers for epithelial ovarian cancer (OVCA) as they encapsulate vital information. Interestingly, exosomes are enriched in small non-coding RNAs (i.e. miRNAs) which can be transferred to other cells to regulate several biological processes. We aimed to profile the exosomal content to identify trends associated with miRNAs across the different stages of disease and examine the effect of these exosomes on fibroblast cells.

Methods: Exosomes were isolated from benign and epithelial ovarian cancer patient plasma (n=127) and characterised. A small RNA library was prepared and the expression of specific miRNAs was validated using RT-qPCR. Fibroblast cells were treated with these exosomes and the expression of specific miRNAs was determined in addition to cell proliferation and migration.

Results: Exosomal miRNAs demonstrated either an increase or a decrease in expression with advancing cancer progression. 119 miRNAs were found to be differentially expressed across disease stages (p<0.05), determined using likelihood ratio tests. A specific set of miRNAs (miR-22-3p, miR-766-3p, miR-340-3p, miR-379-3p, miR-10a-5p, miR-30a-5p, miR-126-5p, miR-26a-1-5p and miR-181a-1-5p) which increase in association with OVCA progression were identified. Exosomes are able to transfer these miRNAs to fibroblasts to increase their migration and proliferation.

Conclusions: We propose that exosomes, present in the circulation of patients with OVCA, transfer specific oncogenic miRNAs to cells present in the tumour microenvironment to promote cancer progression.