New functions for the cellular oxygen sensor PHD3 in clear cell renal cell carcinoma Article Swipe
The family of HIF prolyl hydroxylase enzymes (PHDs) is known for their function of post-translationally regulating hypoxia-inducible transcription factors (HIFs) in oxygen-dependent manner. HIFs are the key transcription factors mediating the cellular responses to low oxygen concentration, i.e. hypoxia, by activating target genes that in turn drive the cellular adaptation. Among the PHDs, PHD3 shows particularly high expression in clear cell renal cell carcinoma (ccRCC) tumors and derived cell lines. However, the role of PHD3 expression in ccRCC has remained elusive. In this thesis work, PHD3 is shown to have widespread functions in ccRCC. PHD3 regulates glucose metabolism and lactate production, as well as number of translational machinery components and activation of mTOR downstream signaling. PHD3 has previously been linked to cell cycle progression and my work extended the knowledge on PHD3 enhancing cell cycle progression, proliferation and 3D colony formation in ccRCC cells. PHD3 was also found to regulate cell migration and several proteins related to cytoskeleton and attachment. Moreover, the work revealed a novel mechanism for HIF-2α post-transcriptional regulation as PHD3 was found to maintain HIF-2α mRNA level in ccRCC cells. This new relation of PHD3 and HIF2A was further examined in clinical ccRCC tumor samples, in which a positive correlation of HIF2A and PHD3 expression was demonstrated. The results indicate a substantial role for PHD3 in promoting ccRCC growth and other processes linked to malignant progression
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Metadata
- Type
- article
- Language
- en
- Landing Page
- http://www.utupub.fi/handle/10024/144890
- http://www.utupub.fi/handle/10024/144890
- OA Status
- green
- Related Works
- 20
- OpenAlex ID
- https://openalex.org/W2802389981
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2802389981Canonical identifier for this work in OpenAlex
- Title
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New functions for the cellular oxygen sensor PHD3 in clear cell renal cell carcinomaWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2018Year of publication
- Publication date
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2018-05-18Full publication date if available
- Authors
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Petra MiikkulainenList of authors in order
- Landing page
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https://www.utupub.fi/handle/10024/144890Publisher landing page
- PDF URL
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https://www.utupub.fi/handle/10024/144890Direct link to full text PDF
- Open access
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.utupub.fi/handle/10024/144890Direct OA link when available
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Cell, Renal cell carcinoma, Oxygen, Carcinoma, Chemistry, Cell biology, Biology, Internal medicine, Medicine, Biochemistry, Organic chemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- Related works (count)
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20Other works algorithmically related by OpenAlex
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