The role of miRNA regulation in response to hypoxia in gliomasTools Smith, Louise (2023) The role of miRNA regulation in response to hypoxia in gliomas. PhD thesis, University of Nottingham.
AbstractGlioblastoma multiforme (GBM) is the most aggressive and frequent adult brain tumour. Current therapy consists of debulking surgery followed by radiotherapy and temozolomide chemotherapy. The median survival is only 14 months post-therapy due to the high rates of recurrence. GBMs are known to be very heterogenous both within the tumour and between patients, this is a key contributor to GBM recurrence. Solid tumours, including GBM, often harbour hypoxic regions which are areas of low oxygen, often around 1% or lower. Physiologically, the brain is usually at 7% oxygen and can vary often between 12.5% and 2.5%. Hypoxia is a tumour microenvironment which is known to exacerbate and accelerate tumorigenesis. As tumours proliferate and become denser, a hypoxic gradient occurs with less oxygenated cells at the core and more oxygenated cells towards the periphery. Although hypoxic pockets can be found throughout the tumour. Hypoxia causes hypoxia-induced transcription which consequently up or downregulates genes that are important within different hallmarks of cancer. These processes are regulated by many factors including miRNAs. miRNAs are small non-coding sequences which bind to complimentary sequences which cleaves target mRNA and subsequently causes mRNA degradation, translation inhibition or deadenylation. miRNAs regulate gene expression; however, their expression can be affected by many microenvironmental conditions such as hypoxia.
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