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Full Text, Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Medical Science, Griffith Health, A variety of factors such as genetic and epigenetic alterations is known to be involved in initiation and progression of the malignant lesion. microRNA dysregulation is identified as one of the epigenetic changes during cancer development. They play important roles in modulating range of pathways including cell differentiation apoptosis, cell invasion, Epithelial-mesenchymal transition (EMT) and angiogenesis. Angiogenesis is a vital process for cancer survival. The process of angiogenesis in malignancy is initially and mainly promoted by vascular endothelial growth factors (VEGFs). Over-expression of VEGF-A in different carcinomas has been reported, and its cross-talk has been described in cancer between angiogenesis and epithelial-to-mesenchymal transition (EMT) process. EMT is a process which generates motile and invasive cells and converts epithelial cells into mesenchymal cells. Subsequently, cells acquire migratory abilities, accumulate resistance to different types of cancer therapies and gain stem-cell like properties.

Full Text, Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Medical Science, Griffith Health, Cancer is a disease driven by complex genetic abnormalities. The ultimate outcome of these complex genetic disorders is uncontrolled cell proliferation. There are two major cellular proliferation and survival signalling pathways which are RAS-RAF- MEK-ERK and PI3K-AKT-mTOR proliferation-survival pathways. These proliferation-survival cell signalling pathways receive, carry and transfer important cell signals to the nucleus where the major transcription changes required for cell proliferation and survival occur. In normal cells, this proliferation cell signalling process is controlled, but this process becomes uncontrolled in cancer cells due to complex genetic changes like genetic mutations. One such genetic mutation is the BRAF V600E mutation which transforms the BRAF kinase into an auto-activated kinase. As a result, the RAS-RAF-MEK-ERK proliferation-survival pathway becomes truncated and auto-activated BRAF kinase continuously sends proliferation-survival signals to the nucleus through downstream MEK-ERK signalling molecules. Therefore, BRAF V600E mutated cells proliferate without control, invade & damage surrounding tissues and metastasise all over the body.