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Effect of AKR1B10 expression on metabolic plasticity in liver cancer cells
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Nisan Korkmaz Tez (2).pdf
Date
2024-1-18
Author
Korkmaz, Nisan
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Aldo-keto reductases (AKRs) constitute a diverse group of oxidoreductases proficient in utilizing electrons from NADPH to reduce a broad spectrum of substrates. Among these, Aldo-Keto Reductase 1B10 (AKR1B10) stands as a pivotal metabolic enzyme implicated in cellular metabolism, particularly in the reduction of carbonyl substrates and the detoxification of reactive species generated during lipid oxidation. In the context of hepatocellular carcinoma (HCC), the role and impact of AKR1B10, particularly in the context of cancer metabolism, is currently unknown. This thesis aimed to uncover the metabolic implications of AKR1B10 expression in HuH-7 cells, focusing on its influence on oxidative metabolism, cellular survival under stress conditions, and broader metabolic alterations. Through the utilization of stable AKR1B10-overexpressing HuH-7 cells and empty vector transfected control cells, we observed that AKR1B10 expression led to distinct alterations in metabolic pathways, including increased activation of nutrient-sensing pathways, suggestive of reprogramming of cellular metabolism. AKR1B10 expression led to increased cell death under hypoxic conditions, indicating a critical reliance on oxygen for survival. Under glucose deprivation, AKR1B10 expressing cells showed decreased cellular motility. An untargeted metabolomics assay revealed altered levels of fatty acids in AKR1B10 expressing cells. These findings collectively suggest an impact of AKR1B10 expression on altered metabolism and survival characteristics of liver cancer cells.
Subject Keywords
Hepatocellular carcinoma
,
AKR1B10
,
Metabolomics
URI
https://hdl.handle.net/11511/108763
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Graduate School of Natural and Applied Sciences, Thesis
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N. Korkmaz, “Effect of AKR1B10 expression on metabolic plasticity in liver cancer cells,” M.S. - Master of Science, Middle East Technical University, 2024.