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Role of miR-526b and miR-655 in breast cancer
Ugwuagbo, Kingsley ChukwunonsoMajumder, Mousumi
Brandon University, Faculty of Science
x, 78 pages : color illustrations
Thesis chapters are cowritten with other researchers, including the thesis supervisor, Dr. Mousumi Majumder.
Includes bibliographical references (pages 65-72).
"In partial fulfillment of the requirements for the degree of Master of Science, Evironmental and Life Sciences."
Breast cancer is the most prevalent organ-specific cancer in women world-wide. Angiogenesis is the formation of new blood vessels from pre-existing ones. This biological process plays a major role in tumor metastasis and progression. Small RNA molecules (microRNAs or miRNAs) are found to regulate tumor metastasis and can be identified in the body fluids. The first thesis manuscript (2nd chapter), investigated the roles of miR-526b and miR-655 in breast cancer-associated angiogenesis. Here, I measured the mRNA expression of known angiogenesis and lymphangiogenesis markers in the miRNA overexpressed breast cancer cell lines. The roles of both miRNAs on human umbilical vein endothelial cell (HUVEC) functions, using conditioned media collected from the cancer cell lines were also tested. The results show that both miRNAs promote the upregulation of angiogenesis and lymphangiogenesis ligands, VEGFA, VEGFC, VEGFD and the vascular growth factor receptors, VEGFR1 [and] VEGFR2 at mRNA level. Moreover, the cell-free conditioned media from the miRNA overexpressed cancer cells promote migration and tube formation of HUVEC in vitro via EP4 activation. Hence, both miRNAs regulate tumor growth and paracrine stimulation of angiogenesis in breast cancer. Moreover, we have previously shown that miR-526b and miR-655 are significantly high in human breast tumors and correlate with poor patient survival. However, these two miRNAs were never tested in human blood plasma. The second manuscript (3rd chapter), tested the expression levels of pri-miR526b and pri-miR655 in the blood plasma of breast cancer patients and benign candidates with no evidence of disease (control). Results show that pri-miRNA in plasma are significantly high in breast cancer than the control. Also, both pri-miRNAs can differentiate tumor stages and associates with diagnostic parameters in breast cancer. This suggests the potential of these pri-miRNAs as a blood-based biomarker in breast cancer.
Brandon University.Faculty of Science