ArticleScientific reports2019
PIN1 transcript variant 2 acts as a long non-coding RNA that controls the HIF-1-driven hypoxic response.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Pin1 as a central node in oncogenic signaling: Mechanistic insights and clinical prospects (Review).Molecular medicine reports · 2025Review
- SPATA20 deficiency enhances the metastatic and angiogenic potential of cancer cells by promoting HIF-1α synthesis.American journal of cancer research · 2024Article
- Chronic airway epithelial hypoxia exacerbates injury in muco-obstructive lung disease through mucus hyperconcentration.Science translational medicine · 2023Article
- Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation.Life (Basel, Switzerland) · 2022Review
- Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting.World journal of stem cells · 2021Review
- Hypoxia-induced alternative splicing in human diseases: the pledge, the turn, and the prestige.Cellular and molecular life sciences : CMLS · 2021Review
- Hypoxia-Induced Non-Coding RNAs Controlling Cell Viability in Cancer.International journal of molecular sciences · 2021Review
- Loss of EGR3 is an independent risk factor for metastatic progression in prostate cancer.Oncogene · 2020Article
- Long-Noncoding RNA (lncRNA) in the Regulation of Hypoxia-Inducible Factor (HIF) in Cancer.Non-coding RNA · 2020Review
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
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Authors and funding
4 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor HIF-1 induces the expression of genes that are essential for cell survival and oxygen homeostasis in hypoxic conditions. The prolyl isomerase Pin1 plays a role in the regulation of HIF-1α. However, the mechanism by which Pin1 controls HIF-1α remains controversial. Surprisingly, we here show that a PIN1 transcript downregulates HIF-1α as a long non-coding RNA. Pin1-silencing siRNAs augmented the hypoxia-induced expression of HIF-1α, thereby upregulating the expression of HIF-1 target genes. However, the overexpression of Pin1 protein did not inhibit the hypoxic expression of HIF-1α. Pin1 restoration in Pin1-depleted cells also failed to reverse the induction of HIF-1α by Pin1 knockdown. Unexpectedly, HIF-1α was found to be induced by both siRNAs for PIN1 transcript variants 1/2 and that for PIN1 transcript variants 2/3, indicating that the PIN1 transcript variant 2 (PIN1-v2) is responsible for HIF-1α induction. Mechanistically, PIN1-v2, which is classified as a long non-coding RNA due to early termination of translation, was evaluated to inhibit the transcription of HIF1A gene. In conclusion, PIN1-v2 may function in balancing the HIF-1-driven gene expression under hypoxia.
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