ArticleMolecular cancer research : MCR2014
Hypoxia regulates alternative splicing of HIF and non-HIF target genes.
Article in Molecular cancer research : MCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- Review
- PFV Tas protein recruits hnRNPF to promote the splicing of tas/bet pre-mRNA.Cell & bioscience · 2026Article
- Targeting ferroptosis for precision medicine in cervical cancer.Apoptosis : an international journal on programmed cell death · 2025Review
- Biological function of RNA-binding proteins in myocardial infarction: a potential emerging therapeutic limelight.Cell & bioscience · 2025Review
- Association betweenFrontiers in medicine · 2025Article
- EPAS1, a hypoxia- and ferroptosis-related gene, promotes malignant behaviour of cervical cancer by ceRNA and super-enhancer.Journal of cellular and molecular medicine · 2024Article
- A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway.Molecular cancer · 2024Article
- Alternative splicing of CEACAM1 by hypoxia-inducible factor-1α enhances tolerance to hepatic ischemia in mice and humans.Science translational medicine · 2023Article
- Poison cassette exon splicing of SRSF6 regulates nuclear speckle dispersal and the response to hypoxia.Nucleic acids research · 2023Article
- Chronic hypoxia is associated with transcriptomic reprogramming and increased genomic instability in cancer cells.Frontiers in cell and developmental biology · 2023Article
- Oncometabolism: A Paradigm for the Metabolic Remodeling of the Failing Heart.International journal of molecular sciences · 2022Review
- Targeting HIF-1α/NOTCH1 pathway eliminates CD44Oncogene · 2022Article
- Review
- Identification of novel mutations and functional impacts of EPAS1 in colorectal cancer.Cancer medicine · 2021Article
- Hypoxia-induced alternative splicing in human diseases: the pledge, the turn, and the prestige.Cellular and molecular life sciences : CMLS · 2021Review
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- Molecular Deregulation ofFrontiers in oncology · 2020Article
- A combined computational pipeline to detect circular RNAs in human cancer cells under hypoxic stress.Journal of molecular cell biology · 2019Article
- Regulation of Gene Expression under Hypoxic Conditions.International journal of molecular sciences · 2019Review
- SIRT3 elicited an anti-Warburg effect through HIF1α/PDK1/PDHA1 to inhibit cholangiocarcinoma tumorigenesis.Cancer medicine · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledHypoxia is a common characteristic of many solid tumors. The hypoxic microenvironment stabilizes hypoxia-inducible transcription factor 1α (HIF1α) and 2α (HIF2α/EPAS1) to activate gene transcription, which promotes tumor cell survival. The majority of human genes are alternatively spliced, producing RNA isoforms that code for functionally distinct proteins. Thus, an effective hypoxia response requires increased HIF target gene expression as well as proper RNA splicing of these HIF-dependent transcripts. However, it is unclear if and how hypoxia regulates RNA splicing of HIF targets. This study determined the effects of hypoxia on alternative splicing (AS) of HIF and non-HIF target genes in hepatocellular carcinoma cells and characterized the role of HIF in regulating AS of HIF-induced genes. The results indicate that hypoxia generally promotes exon inclusion for hypoxia-induced, but reduces exon inclusion for hypoxia-reduced genes. Mechanistically, HIF activity, but not hypoxia per se is found to be necessary and sufficient to increase exon inclusion of several HIF targets, including pyruvate dehydrogenase kinase 1 (PDK1). PDK1 splicing reporters confirm that transcriptional activation by HIF is sufficient to increase exon inclusion of PDK1 splicing reporter. In contrast, transcriptional activation of a PDK1 minigene by other transcription factors in the absence of endogenous HIF target gene activation fails to alter PDK1 RNA splicing. IMPLICATIONS: This study demonstrates a novel function of HIF in regulating RNA splicing of HIF target genes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.