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Measuring mRNA Levels Over Time During the Yeast S. cerevisiae Hypoxic Response
Published on: August 10, 2017
Hypoxic regulation of mRNA expression
Lawrence B Gardner1, Paul G Corn
1New York University School of Medicine and MD Anderson Cancer Center, USA. lawrence.gardner@med.nyu.edu
Abstract:
Many tumors are hypoxic, and cells that are experimentally rendered hypoxic display a variety of phenotypes which allow them to adapt to the micro-environment. These phenotypes include a shift from aerobic to anaerobic metabolism, a diminution of reactive oxygen species, an arrest of proliferation, apoptosis, and a secretion of pro-angiogenic growth factors. Some of these hypoxic phenotypes are re-capitulated in normoxic tumor cells (e.g., an increase in anaerobic metabolism), and some tumors have undergone mutations that allow them to bypass the cell cycle arrest and apoptosis typically seen in hypoxic cells. Hypoxic regulation of gene expression is responsible for many hypoxia-induced phenotypes, and here we review a variety of mechanisms by which gene expression is altered in hypoxic cells. These include transcription by HIF-1, the hypoxia inducible transcription factor, and other hypoxia-inducible transcription factors, including ones generated by hypoxic activation of the integrated stress response. Recent data from our laboratory demonstrate that nonsense mediated RNA decay is also regulated in hypoxic cells and thus may play an important role in hypoxic gene regulation and hypoxic phenotypes.
Insights
Tumor cells adapt to low oxygen (hypoxia) by altering metabolism and gene expression. This review explores how hypoxia-inducible factors and RNA decay regulate these adaptive phenotypes in cancer.
Area of Science:
- Molecular Biology
- Cancer Research
- Cellular Physiology
Background:
- Tumor hypoxia is a common characteristic of solid tumors.
- Hypoxic conditions induce diverse cellular phenotypes crucial for tumor survival and adaptation.
- These phenotypes include metabolic shifts, altered proliferation, and secretion of growth factors.
Purpose of the Study:
- To review the mechanisms of gene expression regulation in hypoxic cells.
- To highlight the role of hypoxia-inducible transcription factors (HIFs) in mediating hypoxia-induced phenotypes.
- To discuss the emerging role of nonsense-mediated RNA decay in hypoxic gene regulation.
Main Methods:
- Literature review of studies on tumor hypoxia and gene expression.
- Analysis of established and emerging mechanisms of transcriptional and post-transcriptional regulation.
- Inclusion of recent laboratory data on nonsense-mediated RNA decay in hypoxia.
Main Results:
- Hypoxia-inducible transcription factors, primarily HIF-1, are key regulators of gene expression under low oxygen.
- Other transcription factors, activated by the integrated stress response, also contribute to hypoxic gene regulation.
- Nonsense-mediated RNA decay is identified as a novel regulatory mechanism influenced by hypoxia.
Conclusions:
- Altered gene expression is central to the adaptive phenotypes observed in hypoxic tumor cells.
- Understanding HIF-mediated and RNA decay pathways provides insights into tumor adaptation.
- Further research into these regulatory mechanisms can reveal new therapeutic targets for hypoxic tumors.
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