An investigation into the effect of p53, miRNA-22, and MTHFD2 in cancer metabolism
File(s)
Author(s)
Yang, Tianlai
Type
Thesis
Abstract
The effect of cell regulators on cancer metabolism can affect cancer growth. The link between the transcription factor p53, a microRNA (miRNA) with regulatory effects on cancer growth - miRNA-22, and a cancer-related metabolic enzyme MTHFD2 was explored in cancer cells. Although there was no clear link between these three factors, the effect of each individual component on cancer cell metabolism did produce interesting findings. The absence of p53 increased intermediates involved in nucleotide synthesis and reduce substrates required for glutathione synthesis in the mouse model. Overexpression of miRNA-22 at physiological levels increased glucose uptake, lactate production, and biosynthesis of serine, glycine and glycerol-3-phosphate in breast cancer cells. Knockdown of MTHFD2 caused breast cancer cells to be more reliant on exogenous glycine. The complexity of cell biology means that there is still much to be understood, and this work can hopefully contribute to ongoing research in this area.
Version
Open Access
Date Issued
2017-06
Date Awarded
2017-11
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Keun, Hector
Gooderham, Nigel
Sponsor
Medical Research Council (Great Britain)
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)