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Extracellular vesicle miRNAs are regulators of lung adenocarcinoma tumor progression and are important tumor-stromal communicators

University of British Columbia

Lung adenocarcinoma (LAC) is the most common subtype of non-small cell lung cancer and is the leading cause of cancer death worldwide. Five-year survival rates of LAC remain dismally low at ~17%, due to the late stage of diagnosis. MicroRNAs (miRNAs) are small RNAs 17-22 nucleotides long and are stable within the serum and when present within extracellular vesicles (EVs), additionally EV miRNAs contribute to tumor-stromal communication. Determining non-invasive novel biomarkers for early disease detection and understanding EV miRNA tumor-stromal communication may aid in improving overall survival. In this thesis, I identify miRNAs that are differentially detected within the serum of patients with LAC using miRNA profiling of patient serum samples and demographically matched controls. I additionally characterize the function of LAC secreted miRNA within EVs when entering normal fibroblast and endothelial cells. My hypotheses are that miRNAs within the serum of LAC patients will show a unique signature that will be distinguishable from non-cancer high risk individuals, and that miRNAs selectively released from LAC cells within EVs will promote tumorigenesis in endothelial cells through stimulating angiogenesis and in fibroblasts through promoting the cancer associated fibroblast phenotype. A unique signature of miRNAs within the serum of LAC patients is found and miRNAs within patient serum is dependent on sex. Several miRNAs within LAC EVs are then functionally characterized in the role they play when signaling to normal stromal cells. Together, this thesis provides a comprehensive analysis of LAC miRNAs and the roles they play as biomarkers within the serum and as tumor-stromal signals when within EVs.

Text

2018-04-19

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/65512

Interdisciplinary Oncology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/